Virology
Encyclopedia
Virology is the study of virus
es and virus-like agents: their structure, classification and evolution, their ways to infect and exploit cells
for virus reproduction, the diseases they cause, the techniques to isolate and culture them, and their use in research and therapy. Virology is often considered a part of microbiology
or of medicine
.
. Viruses can be classified according to the host cell they infect: animal viruses, plant virus
es, fungal
viruses, and bacteriophage
s (viruses infecting bacteria
, which include the most complex viruses). Another classification uses the geometrical shape of their capsid
(often a helix
or an icosahedron
) or the virus's structure (e.g. presence or absence of a lipid
envelope
). Viruses range in size from about 30 nm
to about 450 nm
, which means that most of them cannot be seen with light microscopes. The shape and structure of viruses has been studied by electron microscopy
, NMR spectroscopy
, and X-ray crystallography
.
The most useful and most widely used classification system distinguishes viruses according to the type of nucleic acid
they use as genetic material and the viral replication
method they employ to coax host cells into producing more viruses:
In addition virologists also study subviral particles, infectious entities even smaller than viruses: viroid
s (naked circular RNA molecules infecting plants), satellites
(nucleic acid molecules with or without a capsid that require a helper virus for infection and reproduction), and prion
s (protein
s that can exist in a pathological conformation that induces other prion molecules to assume that same conformation).
The latest report by the International Committee on Taxonomy of Viruses
(2005) lists 5450 viruses, organized in over 2,000 species, 287 genera, 73 families and 3 orders.
The taxa
in virology are not necessarily monophyletic. In fact, the evolutionary relationships of the various virus groups remain unclear, and three hypotheses regarding their origin exist:
It is of course possible that different alternatives apply to different virus groups.
Of particular interest here is mimivirus
, a giant virus that infects amoebae
and carries much of the molecular machinery traditionally associated with bacteria. Is it a simplified version of a parasitic prokaryote, or did it originate as a simpler virus that acquired genes from its host?
The evolution of viruses, which often occurs in concert with the evolution of their hosts, is studied in the field of viral evolution.
While viruses reproduce and evolve, they don't engage in metabolism
and depend on a host cell for reproduction. The often-debated question of whether they are alive or not is a matter of definition that does not affect the biological reality of viruses.
, influenza
, rabies
, measles
, many forms of diarrhea
, hepatitis
, yellow fever
, polio
, smallpox
and AIDS
. Herpes simplex
causes cold sores and genital herpes and is under investigation as a possible factor in Alzheimer's
.
Some viruses, known as oncovirus
es, contribute to certain forms of cancer
. The best studied example is the association between Human papillomavirus
and cervical cancer
: it is now acknowledged that almost all cases of cervical cancer are caused by certain strains of this sexually transmitted virus. Another example is infection with hepatitis B and hepatitis C
viruses, which are associated with liver cancer
.
Some subviral particles also cause disease: the transmissible spongiform encephalopathies
, which include Kuru
, Creutzfeldt-Jakob disease
and bovine spongiform encephalopathy
("mad cow disease"), are caused by prions, and hepatitis D
is due to a satellite virus.
The study of the manner in which viruses cause disease is viral pathogenesis
. The degree to which a virus causes disease is its virulence
.
When the immune system
of a vertebrate
encounters a virus, it produces specific antibodies
which bind to the virus and mark it for destruction. The presence of these antibodies is often used to determine whether a person has been exposed to a given virus in the past, with tests such as ELISA
. Vaccination
s protect against viral diseases, in part, by eliciting the production of antibodies. Specifically constructed monoclonal antibodies
can also be used to detect the presence of viruses, with a technique called fluorescence microscopy.
A second defense of vertebrates against viruses, cell-mediated immunity
, involves immune cells known as T cell
s: the body's cells constantly display short fragments of their proteins on the cell's surface, and if a T cell recognizes a suspicious viral fragment there, the host cell is destroyed and the virus-specific T-cells proliferate. This mechanism is jump-started by certain vaccinations.
RNA interference
, an important cellular mechanism found in plants, animals and many other eukaryote
s, most likely evolved as a defense against viruses. An elaborate machinery of interacting enzymes detects double-stranded RNA molecules (which occur as part of the life cycle of many viruses) and then proceeds to destroy all single-stranded versions of those detected RNA molecules.
Every lethal viral disease presents a paradox: killing its host is obviously of no benefit to the virus, so how and why did it evolve to do so? Today it is believed that most viruses are relatively benign in their natural hosts; the lethal viral diseases are explained as resulting from an "accidental" jump of the virus from a species in which it is benign to a new one that is not accustomed to it (see zoonosis
). For example, serious influenza viruses probably have pigs or birds as their natural host, and HIV
is thought to derive from the benign non-human primate virus SIV
.
While it has been possible to prevent (certain) viral diseases by vaccination for a long time, the development of antiviral drug
s to treat viral diseases is a comparatively recent development. The first such drug was interferon
, a substance that is naturally produced by certain immune cells when an infection is detected and stimulates other parts of the immune system.
s, the viruses which infect bacteria
, can be relatively easily grown as viral plaque
s on bacterial cultures
. Bacteriophages occasionally move genetic material from one bacterial cell to another in a process known as transduction
, and this horizontal gene transfer
is one reason why they served as a major research tool in the early development of molecular biology
. The genetic code
, the function of ribozyme
s, the first recombinant DNA
and early genetic libraries
were all arrived at using bacteriophages. Certain genetic elements derived from viruses, such as highly effective promoters, are commonly used in molecular biology research today.
Growing animal viruses outside of the living host animal is more difficult. Classically, fertilized chicken eggs have often been used, but cell culture
s are increasingly employed for this purpose today.
Since some viruses that infect eukaryote
s need to transport their genetic material into the host cell's nucleus
, they are attractive tools for introducing new genes into the host (known as transformation
or transfection
). Modified retroviruses are often used for this purpose, as they integrate their genes into the host's chromosome
s.
This approach of using viruses as gene vectors is being pursued in the gene therapy
of genetic diseases. An obvious problem to be overcome in viral gene therapy is the rejection of the transforming virus by the immune system.
Phage therapy
, the use of bacteriophages to combat bacterial diseases, was a popular research topic before the advent of antibiotics and has recently seen renewed interest.
Oncolytic virus
es are viruses that preferably infect cancer
cells. While early efforts to employ these viruses in the therapy of cancer failed, there have been reports in 2005 and 2006 of encouraging preliminary results.
was recently described; see the uses of viruses in material science and nanotechnology. For a use in mapping neuron
s see the applications of pseudorabies in neuroscience.
sufferers in order to immunize others. In 1717 Lady Mary Wortley Montagu
observed the practice in Istanbul
and attempted to popularize it in Britain, but encountered considerable resistance. In 1796 Edward Jenner
developed a much safer method, using cowpox
to successfully immunize a young boy against smallpox, and this practice was widely adopted. Vaccinations against other viral diseases followed, including the successful rabies
vaccination by Louis Pasteur
in 1886. The nature of viruses however was not clear to these researchers.
In 1892 Dimitri Ivanovski
showed that a disease of tobacco plants
, tobacco mosaic disease
, could be transmitted by extracts that were passed through filters fine enough to exclude even the smallest known bacteria. In 1898 Martinus Beijerinck
, also working on tobacco plants, found that this "filterable agent" grew in the host and was thus not a mere toxin
. The question of whether the agent was a "living fluid" or a particle was however still open.
In 1903 it was suggested for the first time that transduction
by viruses might cause cancer. Such an oncovirus
in chickens was described by Francis Peyton Rous
in 1911; it was later called Rous sarcoma virus 1
and understood to be a retrovirus
. Several other cancer-causing retroviruses have since been described.
The existence of viruses that infect bacteria (bacteriophages) was first recognized by Frederick Twort
in 1911, and, independently, by Felix d'Herelle
in 1917. Since bacteria could be grown easily in culture, this led to an explosion of virology research.
The cause of the devastating Spanish flu
pandemic of 1918 was initially unclear. In late 1918, French scientists showed that a "filter-passing virus" could transmit the disease to people and animals, fulfilling Koch's postulates
.
While plant viruses and bacteriophages can be grown comparatively easily, animal viruses normally require a living host animal, which complicates their study immensely. In 1931 it was shown that influenza virus could be grown in fertilized chicken eggs, a method that is still used today to produce vaccines. In 1937, Max Theiler
managed to grow the yellow fever
virus in chicken eggs and produced a vaccine from an attenuated virus strain; this vaccine saved millions of lives and is still being used today.
Max Delbrück
, an important investigator in the area of bacteriophages, described the basic life cycle of a virus in 1937: rather than "growing", a virus particle is assembled from its constituent pieces in one step; eventually it leaves the host cell to infect other cells. The Hershey-Chase experiment
in 1952 showed that only DNA
and not protein enters a bacterial cell upon infection with bacteriophage T2
. Transduction
of bacteria by bacteriophages was first described in the same year.
In 1949 John F. Enders, Thomas Weller
and Frederick Robbins reported that they had been able to grow poliovirus
in cultured human embryonal cells, the first significant example of an animal virus grown outside of animals or chicken eggs. This work aided Jonas Salk
in deriving a polio vaccine from killed polio viruses; this vaccine was shown to be effective in 1955.
The first virus that could be crystal
ized and whose structure could therefore be elucidated in detail was tobacco mosaic virus
(TMV), the virus that had been studied earlier by Ivanovski and Beijerink. In 1935, Wendell Stanley
achieved its crystallization for electron microscopy
and showed that it remains active even after crystallization. Clear X-ray diffraction pictures of the crystallized virus were obtained by Bernal and Fankuchen in 1941. Based on such pictures, Rosalind Franklin
proposed the full structure of the tobacco mosaic virus in 1955. Also in 1955, Heinz Fraenkel-Conrat and Robley Williams showed that purified TMV RNA
and its capsid
(coat) protein can assemble by themselves to form functional viruses, suggesting that this simple mechanism is likely the natural assembly mechanism within the host cell, as Delbrück had proposed earlier.
In 1963, the Hepatitis B virus was discovered by Baruch Blumberg who went on to develop a vaccine against Hepatitis B.
In 1965, Howard Temin described the first retrovirus
: an RNA-virus that was able to insert its genome in the form of DNA into the host's genome. Reverse transcriptase
, the key enzyme that retroviruses use to translate their RNA into DNA, was first described in 1970, independently by Howard Temin and David Baltimore
. The first retrovirus infecting human
s was identified by Robert Gallo
in 1974. Later it was found that reverse transcriptase is not specific to retroviruses; retrotransposon
s which code for reverse transcriptase are abundant in the genomes of all eukaryotes. About 10-40% of the human genome derives from such retrotransposons.
In 1975 the functioning of oncoviruses was clarified considerably. Until that time, it was thought that these viruses carried certain genes called oncogene
s which, when inserted into the host's genome, would cause cancer. Michael Bishop
and Harold Varmus showed that the oncogene of Rous sarcoma virus
is in fact not specific to the virus but is contained in the genome of healthy animals of many species. The oncovirus can switch this pre-existing benign proto-oncogene on, turning it into a true oncogene that causes cancer.
1976 saw the first recorded outbreak of Ebola hemorrhagic fever, a highly lethal virally transmitted disease.
In 1977, Frederick Sanger
achieved the first complete sequencing of the genome
of any organism, the bacteriophage Phi X 174. In the same year, Richard Roberts
and Phillip Sharp
independently showed that the genes of adenovirus contain intron
s and therefore require gene splicing. It was later realized that almost all genes of eukaryotes have introns as well.
A worldwide vaccination campaign led by the UN World Health Organization
resulted in the eradication of smallpox
in 1979.
In 1982, Stanley Prusiner discovered prion
s and showed that they cause scrapie
.
The first cases of AIDS
were reported in 1981, and HIV
, the retrovirus causing it, was identified in 1983 by Robert Gallo
and Luc Montagnier
. Tests detecting HIV infection by detecting the presence of HIV antibody were developed. Subsequent tremendous research efforts turned HIV into the best studied virus. Human Herpes Virus 8
, the cause of Kaposi's sarcoma
which is often seen in AIDS patients, was identified in 1994. Several antiretroviral drug
s were developed in the late 1990s, decreasing AIDS mortality dramatically in developed countries.
The Hepatitis C virus
was identified using novel molecular cloning
techniques in 1987, leading to screening tests that dramatically reduced the incidence of post-transfusion
hepatitis
.
The first attempts at gene therapy
involving viral vectors began in the early 1980s, when retroviruses were developed that could insert a foreign gene into the host's genome. They contained the foreign gene but did not contain the viral genome and therefore could not reproduce. Tests in mice were followed by tests in human
s, beginning in 1989. The first human studies attempted to correct the genetic disease severe combined immunodeficiency
(SCID), but clinical success was limited. In the period from 1990 to 1995, gene therapy was tried on several other diseases and with different viral vectors, but it became clear that the initially high expectations were overstated. In 1999 a further setback occurred when 18-year-old Jesse Gelsinger
died in a gene therapy trial. He suffered a severe immune response after having received an adenovirus vector. Success in the gene therapy of two cases of X-linked SCID
was reported in 2000.
In 2002 it was reported that poliovirus
had been synthetically assembled in the laboratory, representing the first synthetic organism. Assembling the 7741-base genome from scratch, starting with the virus's published RNA sequence, took about two years. In 2003 a faster method was shown to assemble the 5386-base genome of the bacteriophage Phi X 174 in 2 weeks.
The giant mimivirus
, in some sense an intermediate between tiny prokaryotes and ordinary viruses, was described in 2003 and sequenced
in 2004.
The strain of Influenza A virus subtype H1N1 that killed up to 50 million people during the Spanish flu
pandemic in 1918 was reconstructed in 2005. Sequence information was pieced together from preserved tissue samples of flu victims; viable virus was then synthesized from this sequence. The 2009 flu pandemic
involved another strain of Influenza A H1N1, commonly known as "swine flu".
By 1985, Harald zur Hausen
had shown that two strains of Human papillomavirus
(HPV) cause most cases of cervical cancer
. Two vaccines protecting against these strains were released in 2006.
In 2006 and 2007 it was reported that introducing a small number of specific transcription factor
genes into normal skin cells of mice or human
s can turn these cells into pluripotent stem cell
s, known as Induced Pluripotent Stem Cell
s. The technique uses modified retroviruses to transform the cells; this is a potential problem for human therapy since these viruses integrate their genes at a random location in the host's genome, which can interrupt other genes and potentially causes cancer.
In 2008, Sputnik virophage
was described, the first known virophage: it uses the machinery of a helper virus to reproduce and inhibits reproduction of that helper virus. Sputnik reproduces in amoeba infected by mamavirus
, a relative of the mimivirus mentioned above and the largest known virus to date.
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es and virus-like agents: their structure, classification and evolution, their ways to infect and exploit cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
for virus reproduction, the diseases they cause, the techniques to isolate and culture them, and their use in research and therapy. Virology is often considered a part of microbiology
Microbiology
Microbiology is the study of microorganisms, which are defined as any microscopic organism that comprises either a single cell , cell clusters or no cell at all . This includes eukaryotes, such as fungi and protists, and prokaryotes...
or of medicine
Medicine
Medicine is the science and art of healing. It encompasses a variety of health care practices evolved to maintain and restore health by the prevention and treatment of illness....
.
Virus structure and classification
A major branch of virology is virus classificationVirus classification
Virus classification is the process of naming viruses and placing them into a taxonomic system. Similar to the classification systems used for cellular organisms, virus classification is the subject of ongoing debate and proposals. This is mainly due to the pseudo-living nature of viruses, which...
. Viruses can be classified according to the host cell they infect: animal viruses, plant virus
Plant virus
Plant viruses are viruses that affect plants. Like all other viruses, plant viruses are obligate intracellular parasites that do not have the molecular machinery to replicate without a host. Plant viruses are pathogenic to higher plants...
es, fungal
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...
viruses, and bacteriophage
Bacteriophage
A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...
s (viruses infecting bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, which include the most complex viruses). Another classification uses the geometrical shape of their capsid
Capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
(often a helix
Helix
A helix is a type of smooth space curve, i.e. a curve in three-dimensional space. It has the property that the tangent line at any point makes a constant angle with a fixed line called the axis. Examples of helixes are coil springs and the handrails of spiral staircases. A "filled-in" helix – for...
or an icosahedron
Icosahedron
In geometry, an icosahedron is a regular polyhedron with 20 identical equilateral triangular faces, 30 edges and 12 vertices. It is one of the five Platonic solids....
) or the virus's structure (e.g. presence or absence of a lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
envelope
Viral envelope
Many viruses have viral envelopes covering their protein capsids. The envelopes typically are derived from portions of the host cell membranes , but include some viral glycoproteins. Functionally, viral envelopes are used to help viruses enter host cells...
). Viruses range in size from about 30 nm
1 E-8 m
To help compare different orders of magnitude this page lists lengths between 10−8 and 10−7 metres .Distances shorter than 10 nanometres*10 nm = 10 nanometres = 10−8 metres*10 nm — lower size of tobacco smoke...
to about 450 nm
1 E-7 m
To help compare different orders of magnitude this page lists lengths between 10−7 and 10−6 m .Distances shorter than 100 nm*100 nm — greatest particle size that can fit through a surgical mask...
, which means that most of them cannot be seen with light microscopes. The shape and structure of viruses has been studied by electron microscopy
Electron microscope
An electron microscope is a type of microscope that uses a beam of electrons to illuminate the specimen and produce a magnified image. Electron microscopes have a greater resolving power than a light-powered optical microscope, because electrons have wavelengths about 100,000 times shorter than...
, NMR spectroscopy
NMR spectroscopy
Nuclear magnetic resonance spectroscopy, most commonly known as NMR spectroscopy, is a research technique that exploits the magnetic properties of certain atomic nuclei to determine physical and chemical properties of atoms or the molecules in which they are contained...
, and X-ray crystallography
X-ray crystallography
X-ray crystallography is a method of determining the arrangement of atoms within a crystal, in which a beam of X-rays strikes a crystal and causes the beam of light to spread into many specific directions. From the angles and intensities of these diffracted beams, a crystallographer can produce a...
.
The most useful and most widely used classification system distinguishes viruses according to the type of nucleic acid
Nucleic acid
Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...
they use as genetic material and the viral replication
Viral replication
Viral replication is the term used by virologists to describe the formation of biological viruses during the infection process in the target host cells. Viruses must first get into the cell before viral replication can occur. From the perspective of the virus, the purpose of viral replication is...
method they employ to coax host cells into producing more viruses:
- DNA virusDNA virusA DNA virus is a virus that has DNA as its genetic material and replicates using a DNA-dependent DNA polymerase. The nucleic acid is usually double-stranded DNA but may also be single-stranded DNA . DNA viruses belong to either Group I or Group II of the Baltimore classification system for viruses...
es (divided into double-stranded DNA viruses and the much less common single-stranded DNA viruses), - RNA virusRNA virusAn RNA virus is a virus that has RNA as its genetic material. This nucleic acid is usually single-stranded RNA but may be double-stranded RNA...
es (divided into positive-sense single-stranded RNA viruses, negative-sense single-stranded RNA viruses and the much less common double-stranded RNA viruses), - reverse transcribingReverse transcriptaseIn the fields of molecular biology and biochemistry, a reverse transcriptase, also known as RNA-dependent DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into single-stranded DNA. It also helps in the formation of a double helix DNA once the RNA has been reverse...
viruses (double-stranded reverse-transcribing DNA virusesDsDNA-RT virusDsDNA-RT viruses are the seventh group in the Baltimore virus classification.They are not considered as DNA viruses ,...
and single-stranded reverse-transcribing RNA viruses including retrovirusRetrovirusA retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
es).
In addition virologists also study subviral particles, infectious entities even smaller than viruses: viroid
Viroid
Viroids are plant pathogens that consist of a short stretch of highly complementary, circular, single-stranded RNA without the protein coat that is typical for viruses. The smallest discovered is a 220 nucleobase scRNA associated with the rice yellow mottle sobemovirus...
s (naked circular RNA molecules infecting plants), satellites
Satellite (biology)
A satellite is a subviral agent composed of nucleic acid that depends on the co-infection of a host cell with a helper or master virus for its multiplication. When a satellite encodes the coat protein in which its nucleic acid is encapsidated it is referred to as a satellite virus...
(nucleic acid molecules with or without a capsid that require a helper virus for infection and reproduction), and prion
Prion
A prion is an infectious agent composed of protein in a misfolded form. This is in contrast to all other known infectious agents which must contain nucleic acids . The word prion, coined in 1982 by Stanley B. Prusiner, is a portmanteau derived from the words protein and infection...
s (protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s that can exist in a pathological conformation that induces other prion molecules to assume that same conformation).
The latest report by the International Committee on Taxonomy of Viruses
International Committee on Taxonomy of Viruses
The International Committee on Taxonomy of Viruses is a committee which authorizes and organizes the taxonomic classification of viruses. They have developed a universal taxonomic scheme for viruses and aim to describe all the viruses of living organisms. Members of the committee are considered to...
(2005) lists 5450 viruses, organized in over 2,000 species, 287 genera, 73 families and 3 orders.
The taxa
Taxon
|thumb|270px|[[African elephants]] form a widely-accepted taxon, the [[genus]] LoxodontaA taxon is a group of organisms, which a taxonomist adjudges to be a unit. Usually a taxon is given a name and a rank, although neither is a requirement...
in virology are not necessarily monophyletic. In fact, the evolutionary relationships of the various virus groups remain unclear, and three hypotheses regarding their origin exist:
- Viruses arose from non-living matter, separately from and in parallel to other life forms, possibly in the form of self-reproducing RNARNARibonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
ribozymeRibozymeA ribozyme is an RNA molecule with a well defined tertiary structure that enables it to catalyze a chemical reaction. Ribozyme means ribonucleic acid enzyme. It may also be called an RNA enzyme or catalytic RNA. Many natural ribozymes catalyze either the hydrolysis of one of their own...
s similar to viroidViroidViroids are plant pathogens that consist of a short stretch of highly complementary, circular, single-stranded RNA without the protein coat that is typical for viruses. The smallest discovered is a 220 nucleobase scRNA associated with the rice yellow mottle sobemovirus...
s. - Viruses arose from earlier, more competent cellular life forms that became parasites to host cells and subsequently lost most of their functionality; examples of such tiny parasitic prokaryotes are MycoplasmaMycoplasmaMycoplasma refers to a genus of bacteria that lack a cell wall. Without a cell wall, they are unaffected by many common antibiotics such as penicillin or other beta-lactam antibiotics that target cell wall synthesis. They can be parasitic or saprotrophic. Several species are pathogenic in humans,...
and NanoarchaeaNanoarchaeumNanoarchaeum equitans is a species of tiny microbe, discovered in 2002 in a hydrothermal vent off the coast of Iceland by Karl Stetter. Since it grows in temperatures approaching boiling, it is considered to be a thermophile. Nanoarchaeum appears to be an obligatory symbiont on the archaeon...
. - Viruses arose as parts of the genome of cells, most likely transposonTransposonTransposable elements are sequences of DNA that can move or transpose themselves to new positions within the genome of a single cell. The mechanism of transposition can be either "copy and paste" or "cut and paste". Transposition can create phenotypically significant mutations and alter the cell's...
s or plasmidPlasmidIn microbiology and genetics, a plasmid is a DNA molecule that is separate from, and can replicate independently of, the chromosomal DNA. They are double-stranded and, in many cases, circular...
s, that acquired the ability to "break free" from the host cell and infect other cells.
It is of course possible that different alternatives apply to different virus groups.
Of particular interest here is mimivirus
Mimivirus
Mimivirus is a viral genus containing a single identified species named Acanthamoeba polyphaga mimivirus , or is a group of phylogenetically related large viruses . In colloquial speech, APMV is more commonly referred to as just “mimivirus”...
, a giant virus that infects amoebae
Amoebozoa
The Amoebozoa are a major group of amoeboid protozoa, including the majority that move by means ofinternal cytoplasmic flow. Their pseudopodia are characteristically blunt and finger-like,...
and carries much of the molecular machinery traditionally associated with bacteria. Is it a simplified version of a parasitic prokaryote, or did it originate as a simpler virus that acquired genes from its host?
The evolution of viruses, which often occurs in concert with the evolution of their hosts, is studied in the field of viral evolution.
While viruses reproduce and evolve, they don't engage in metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
and depend on a host cell for reproduction. The often-debated question of whether they are alive or not is a matter of definition that does not affect the biological reality of viruses.
Viral diseases and host defenses
One main motivation for the study of viruses is the fact that they cause many important infectious diseases, among them the common coldCommon cold
The common cold is a viral infectious disease of the upper respiratory system, caused primarily by rhinoviruses and coronaviruses. Common symptoms include a cough, sore throat, runny nose, and fever...
, influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
, rabies
Rabies
Rabies is a viral disease that causes acute encephalitis in warm-blooded animals. It is zoonotic , most commonly by a bite from an infected animal. For a human, rabies is almost invariably fatal if post-exposure prophylaxis is not administered prior to the onset of severe symptoms...
, measles
Measles
Measles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...
, many forms of diarrhea
Diarrhea
Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
, yellow fever
Yellow fever
Yellow fever is an acute viral hemorrhagic disease. The virus is a 40 to 50 nm enveloped RNA virus with positive sense of the Flaviviridae family....
, polio
Poliomyelitis
Poliomyelitis, often called polio or infantile paralysis, is an acute viral infectious disease spread from person to person, primarily via the fecal-oral route...
, smallpox
Smallpox
Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple"...
and AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
. Herpes simplex
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
causes cold sores and genital herpes and is under investigation as a possible factor in Alzheimer's
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
.
Some viruses, known as oncovirus
Oncovirus
An oncovirus is a virus that can cause cancer. This term originated from studies of acutely-transforming retroviruses in the 1950–60s, often called oncornaviruses to denote their RNA virus origin. It now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor...
es, contribute to certain forms of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. The best studied example is the association between Human papillomavirus
Human papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
and cervical cancer
Cervical cancer
Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...
: it is now acknowledged that almost all cases of cervical cancer are caused by certain strains of this sexually transmitted virus. Another example is infection with hepatitis B and hepatitis C
Hepatitis C
Hepatitis C is an infectious disease primarily affecting the liver, caused by the hepatitis C virus . The infection is often asymptomatic, but chronic infection can lead to scarring of the liver and ultimately to cirrhosis, which is generally apparent after many years...
viruses, which are associated with liver cancer
Liver cancer
Liver tumors or hepatic tumors are tumors or growths on or in the liver . Several distinct types of tumors can develop in the liver because the liver is made up of various cell types. These growths can be benign or malignant...
.
Some subviral particles also cause disease: the transmissible spongiform encephalopathies
Transmissible spongiform encephalopathy
Transmissible spongiform encephalopathies , also known as prion diseases, are a group of progressive conditions that affect the brain and nervous system of many animals, including humans. According to the most widespread hypothesis they are transmitted by prions, though some other data suggest an...
, which include Kuru
Kuru (disease)
Kuru is an incurable degenerative neurological disorder that is a type of transmissible spongiform encephalopathy, caused by a prion found in humans...
, Creutzfeldt-Jakob disease
Creutzfeldt-Jakob disease
Creutzfeldt–Jakob disease or CJD is a degenerative neurological disorder that is incurable and invariably fatal. CJD is at times called a human form of mad cow disease, given that bovine spongiform encephalopathy is believed to be the cause of variant Creutzfeldt–Jakob disease in humans.CJD...
and bovine spongiform encephalopathy
Bovine spongiform encephalopathy
Bovine spongiform encephalopathy , commonly known as mad-cow disease, is a fatal neurodegenerative disease in cattle that causes a spongy degeneration in the brain and spinal cord. BSE has a long incubation period, about 30 months to 8 years, usually affecting adult cattle at a peak age onset of...
("mad cow disease"), are caused by prions, and hepatitis D
Hepatitis D
Hepatitis D, also referred to as hepatitis D virus and classified as Hepatitis delta virus, is a disease caused by a small circular enveloped RNA virus. It is one of five known hepatitis viruses: A, B, C, D, and E. HDV is considered to be a subviral satellite because it can propagate only in the...
is due to a satellite virus.
The study of the manner in which viruses cause disease is viral pathogenesis
Viral pathogenesis
Viral pathogenesis is the study of how biological viruses cause diseases in their target hosts, usually carried out at the cellular or molecular level. It is a specialized field of study in virology.-See also:*pathogen*pathogenesis...
. The degree to which a virus causes disease is its virulence
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...
.
When the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
of a vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
encounters a virus, it produces specific antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
which bind to the virus and mark it for destruction. The presence of these antibodies is often used to determine whether a person has been exposed to a given virus in the past, with tests such as ELISA
ELISA
Enzyme-linked immunosorbent assay , is a popular format of a "wet-lab" type analytic biochemistry assay that uses one sub-type of heterogeneous, solid-phase enzyme immunoassay to detect the presence of a substance in a liquid sample."Wet lab" analytic biochemistry assays involves detection of an...
. Vaccination
Vaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...
s protect against viral diseases, in part, by eliciting the production of antibodies. Specifically constructed monoclonal antibodies
Monoclonal antibodies
Monoclonal antibodies are monospecific antibodies that are the same because they are made by identical immune cells that are all clones of a unique parent cell....
can also be used to detect the presence of viruses, with a technique called fluorescence microscopy.
A second defense of vertebrates against viruses, cell-mediated immunity
Cell-mediated immunity
Cell-mediated immunity is an immune response that does not involve antibodies but rather involves the activation of macrophages, natural killer cells , antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in response to an antigen...
, involves immune cells known as T cell
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...
s: the body's cells constantly display short fragments of their proteins on the cell's surface, and if a T cell recognizes a suspicious viral fragment there, the host cell is destroyed and the virus-specific T-cells proliferate. This mechanism is jump-started by certain vaccinations.
RNA interference
RNA interference
RNA interference is a process within living cells that moderates the activity of their genes. Historically, it was known by other names, including co-suppression, post transcriptional gene silencing , and quelling. Only after these apparently unrelated processes were fully understood did it become...
, an important cellular mechanism found in plants, animals and many other eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s, most likely evolved as a defense against viruses. An elaborate machinery of interacting enzymes detects double-stranded RNA molecules (which occur as part of the life cycle of many viruses) and then proceeds to destroy all single-stranded versions of those detected RNA molecules.
Every lethal viral disease presents a paradox: killing its host is obviously of no benefit to the virus, so how and why did it evolve to do so? Today it is believed that most viruses are relatively benign in their natural hosts; the lethal viral diseases are explained as resulting from an "accidental" jump of the virus from a species in which it is benign to a new one that is not accustomed to it (see zoonosis
Zoonosis
A zoonosis or zoonoseis any infectious disease that can be transmitted from non-human animals to humans or from humans to non-human animals . In a study of 1415 pathogens known to affect humans, 61% were zoonotic...
). For example, serious influenza viruses probably have pigs or birds as their natural host, and HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
is thought to derive from the benign non-human primate virus SIV
SIV
SIV or Siv may refer to:* Simian immunodeficiency virus, a virus found in primates and related to HIV* Siv, a character in the children's fiction book series Guardians of Ga'Hoole...
.
While it has been possible to prevent (certain) viral diseases by vaccination for a long time, the development of antiviral drug
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
s to treat viral diseases is a comparatively recent development. The first such drug was interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
, a substance that is naturally produced by certain immune cells when an infection is detected and stimulates other parts of the immune system.
Molecular biology research and viral therapy
BacteriophageBacteriophage
A bacteriophage is any one of a number of viruses that infect bacteria. They do this by injecting genetic material, which they carry enclosed in an outer protein capsid...
s, the viruses which infect bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, can be relatively easily grown as viral plaque
Viral plaque
A viral plaque is a visible structure formed within a cell culture, such as bacterial cultures within some nutrient medium . The bacteriophage viruses replicate and spread, thus generating regions of cell destructions known as plaques....
s on bacterial cultures
Microbiological culture
A microbiological culture, or microbial culture, is a method of multiplying microbial organisms by letting them reproduce in predetermined culture media under controlled laboratory conditions. Microbial cultures are used to determine the type of organism, its abundance in the sample being tested,...
. Bacteriophages occasionally move genetic material from one bacterial cell to another in a process known as transduction
Transduction (genetics)
Transduction is the process by which DNA is transferred from one bacterium to another by a virus. It also refers to the process whereby foreign DNA is introduced into another cell via a viral vector. Transduction does not require cell-to-cell contact , and it is DNAase resistant...
, and this horizontal gene transfer
Horizontal gene transfer
Horizontal gene transfer , also lateral gene transfer , is any process in which an organism incorporates genetic material from another organism without being the offspring of that organism...
is one reason why they served as a major research tool in the early development of molecular biology
Molecular biology
Molecular biology is the branch of biology that deals with the molecular basis of biological activity. This field overlaps with other areas of biology and chemistry, particularly genetics and biochemistry...
. The genetic code
Genetic code
The genetic code is the set of rules by which information encoded in genetic material is translated into proteins by living cells....
, the function of ribozyme
Ribozyme
A ribozyme is an RNA molecule with a well defined tertiary structure that enables it to catalyze a chemical reaction. Ribozyme means ribonucleic acid enzyme. It may also be called an RNA enzyme or catalytic RNA. Many natural ribozymes catalyze either the hydrolysis of one of their own...
s, the first recombinant DNA
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
and early genetic libraries
Library (biology)
In molecular biology, a library is a collection of DNA fragments that is stored and propagated in a population of micro-organisms through the process of molecular cloning...
were all arrived at using bacteriophages. Certain genetic elements derived from viruses, such as highly effective promoters, are commonly used in molecular biology research today.
Growing animal viruses outside of the living host animal is more difficult. Classically, fertilized chicken eggs have often been used, but cell culture
Cell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
s are increasingly employed for this purpose today.
Since some viruses that infect eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...
s need to transport their genetic material into the host cell's nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
, they are attractive tools for introducing new genes into the host (known as transformation
Transformation (genetics)
In molecular biology transformation is the genetic alteration of a cell resulting from the direct uptake, incorporation and expression of exogenous genetic material from its surroundings and taken up through the cell membrane. Transformation occurs naturally in some species of bacteria, but it can...
or transfection
Transfection
Transfection is the process of deliberately introducing nucleic acids into cells. The term is used notably for non-viral methods in eukaryotic cells...
). Modified retroviruses are often used for this purpose, as they integrate their genes into the host's chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
s.
This approach of using viruses as gene vectors is being pursued in the gene therapy
Gene therapy
Gene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...
of genetic diseases. An obvious problem to be overcome in viral gene therapy is the rejection of the transforming virus by the immune system.
Phage therapy
Phage therapy
Phage therapy is the therapeutic use of bacteriophages to treat pathogenic bacterial infections. Although extensively used and developed mainly in former Soviet Union countries circa 1920, this method of therapy is still being tested for treatment of a variety of bacterial and poly-microbial...
, the use of bacteriophages to combat bacterial diseases, was a popular research topic before the advent of antibiotics and has recently seen renewed interest.
Oncolytic virus
Oncolytic virus
An oncolytic virus is a virus that preferentially infects and lyses cancer cells; these have obvious functions for cancer therapy, both by direct destruction of the tumour cells, and, if modified, as vectors enabling genes expressing anticancer proteins to be delivered specifically to the tumor...
es are viruses that preferably infect cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
cells. While early efforts to employ these viruses in the therapy of cancer failed, there have been reports in 2005 and 2006 of encouraging preliminary results.
Other uses of viruses
A new application of genetically engineered viruses in nanotechnologyNanotechnology
Nanotechnology is the study of manipulating matter on an atomic and molecular scale. Generally, nanotechnology deals with developing materials, devices, or other structures possessing at least one dimension sized from 1 to 100 nanometres...
was recently described; see the uses of viruses in material science and nanotechnology. For a use in mapping neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s see the applications of pseudorabies in neuroscience.
History of virology
A very early form of vaccination known as variolation was developed several thousand years ago in China. It involved the application of materials from smallpoxSmallpox
Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple"...
sufferers in order to immunize others. In 1717 Lady Mary Wortley Montagu
Lady Mary Wortley Montagu
The Lady Mary Wortley Montagu was an English aristocrat and writer. Montagu is today chiefly remembered for her letters, particularly her letters from Turkey, as wife to the British ambassador, which have been described by Billie Melman as “the very first example of a secular work by a woman about...
observed the practice in Istanbul
Istanbul
Istanbul , historically known as Byzantium and Constantinople , is the largest city of Turkey. Istanbul metropolitan province had 13.26 million people living in it as of December, 2010, which is 18% of Turkey's population and the 3rd largest metropolitan area in Europe after London and...
and attempted to popularize it in Britain, but encountered considerable resistance. In 1796 Edward Jenner
Edward Jenner
Edward Anthony Jenner was an English scientist who studied his natural surroundings in Berkeley, Gloucestershire...
developed a much safer method, using cowpox
Cowpox
Cowpox is a skin disease caused by a virus known as the Cowpox virus. The pox is related to the vaccinia virus and got its name from the distribution of the disease when dairymaids touched the udders of infected cows. The ailment manifests itself in the form of red blisters and is transmitted by...
to successfully immunize a young boy against smallpox, and this practice was widely adopted. Vaccinations against other viral diseases followed, including the successful rabies
Rabies
Rabies is a viral disease that causes acute encephalitis in warm-blooded animals. It is zoonotic , most commonly by a bite from an infected animal. For a human, rabies is almost invariably fatal if post-exposure prophylaxis is not administered prior to the onset of severe symptoms...
vaccination by Louis Pasteur
Louis Pasteur
Louis Pasteur was a French chemist and microbiologist born in Dole. He is remembered for his remarkable breakthroughs in the causes and preventions of diseases. His discoveries reduced mortality from puerperal fever, and he created the first vaccine for rabies and anthrax. His experiments...
in 1886. The nature of viruses however was not clear to these researchers.
In 1892 Dimitri Ivanovski
Dimitri Ivanovski
Dmitri Iosifovich Ivanovsky was a Russian botanist, one of the discoverers of filterable nature of viruses and thus one of the founders of virology....
showed that a disease of tobacco plants
Tobacco
Tobacco is an agricultural product processed from the leaves of plants in the genus Nicotiana. It can be consumed, used as a pesticide and, in the form of nicotine tartrate, used in some medicines...
, tobacco mosaic disease
Tobacco mosaic virus
Tobacco mosaic virus is a positive-sense single stranded RNA virus that infects plants, especially tobacco and other members of the family Solanaceae. The infection causes characteristic patterns on the leaves . TMV was the first virus to be discovered...
, could be transmitted by extracts that were passed through filters fine enough to exclude even the smallest known bacteria. In 1898 Martinus Beijerinck
Martinus Beijerinck
Martinus Willem Beijerinck was a Dutch microbiologist and botanist. Born in Amsterdam, Beijerinck studied at the Technical School of Delft, where he was awarded the degree of Chemical Engineer in 1872. He obtained his Doctor of Science degree from the University of Leiden in 1877...
, also working on tobacco plants, found that this "filterable agent" grew in the host and was thus not a mere toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
. The question of whether the agent was a "living fluid" or a particle was however still open.
In 1903 it was suggested for the first time that transduction
Transduction (genetics)
Transduction is the process by which DNA is transferred from one bacterium to another by a virus. It also refers to the process whereby foreign DNA is introduced into another cell via a viral vector. Transduction does not require cell-to-cell contact , and it is DNAase resistant...
by viruses might cause cancer. Such an oncovirus
Oncovirus
An oncovirus is a virus that can cause cancer. This term originated from studies of acutely-transforming retroviruses in the 1950–60s, often called oncornaviruses to denote their RNA virus origin. It now refers to any virus with a DNA or RNA genome causing cancer and is synonymous with "tumor...
in chickens was described by Francis Peyton Rous
Francis Peyton Rous
Peyton Rous born in Baltimore, Maryland in 1879 and received his B.A. and M.D. from Johns Hopkins University. He was involved in the discovery of the role of viruses in the transmission of certain types of cancer...
in 1911; it was later called Rous sarcoma virus 1
Rous sarcoma virus
Rous sarcoma virus is a retrovirus and is the first oncovirus to have been described: it causes sarcoma in chickens.As with all retroviruses, it reverse transcribes its RNA genome into cDNA before integration into the host DNA.-History:...
and understood to be a retrovirus
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
. Several other cancer-causing retroviruses have since been described.
The existence of viruses that infect bacteria (bacteriophages) was first recognized by Frederick Twort
Frederick Twort
Frederick William Twort was an English bacteriologist and was the original discoverer in 1915 of bacteriophages . He studied medicine at St Thomas's Hospital, London, was superintendent of the Brown Institute for Animals , and he was also professor of bacteriology at the University of London...
in 1911, and, independently, by Felix d'Herelle
Félix d'Herelle
Félix d'Herelle was a French-Canadian microbiologist, the co-discoverer of bacteriophages and experimented with the possibility of phage therapy.-Early years:...
in 1917. Since bacteria could be grown easily in culture, this led to an explosion of virology research.
The cause of the devastating Spanish flu
Spanish flu
The 1918 flu pandemic was an influenza pandemic, and the first of the two pandemics involving H1N1 influenza virus . It was an unusually severe and deadly pandemic that spread across the world. Historical and epidemiological data are inadequate to identify the geographic origin...
pandemic of 1918 was initially unclear. In late 1918, French scientists showed that a "filter-passing virus" could transmit the disease to people and animals, fulfilling Koch's postulates
Koch's postulates
Koch's postulates are four criteria designed to establish a causal relationship between a causative microbe and a disease. The postulates were formulated by Robert Koch and Friedrich Loeffler in 1884 and refined and published by Koch in 1890...
.
While plant viruses and bacteriophages can be grown comparatively easily, animal viruses normally require a living host animal, which complicates their study immensely. In 1931 it was shown that influenza virus could be grown in fertilized chicken eggs, a method that is still used today to produce vaccines. In 1937, Max Theiler
Max Theiler
Max Theiler was a South African/American virologist. He was awarded the Nobel Prize in Physiology or Medicine in 1951 for developing a vaccine against yellow fever.-Career development:...
managed to grow the yellow fever
Yellow fever
Yellow fever is an acute viral hemorrhagic disease. The virus is a 40 to 50 nm enveloped RNA virus with positive sense of the Flaviviridae family....
virus in chicken eggs and produced a vaccine from an attenuated virus strain; this vaccine saved millions of lives and is still being used today.
Max Delbrück
Max Delbrück
Max Ludwig Henning Delbrück was a German-American biophysicist and Nobel laureate.-Biography:Delbrück was born in Berlin, German Empire...
, an important investigator in the area of bacteriophages, described the basic life cycle of a virus in 1937: rather than "growing", a virus particle is assembled from its constituent pieces in one step; eventually it leaves the host cell to infect other cells. The Hershey-Chase experiment
Hershey-Chase experiment
The Hershey–Chase experiments were a series of experiments conducted in 1952 by Alfred Hershey and Martha Chase, which helped to confirm that DNA was the genetic material. While DNA had been known to biologists since 1869, a few scientists still assumed at the time that proteins carried the...
in 1952 showed that only DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
and not protein enters a bacterial cell upon infection with bacteriophage T2
Enterobacteria phage T2
Enterobacteria phage T2 is a virulent bacteriophage of the T4-like viruses genus, in the family Myoviridae. It infects Escherichia coli and is the best known of the T-even phages. Its virion contains linear double-stranded DNA, terminally redundant and circularly permuted. The phage is covered by a...
. Transduction
Transduction (genetics)
Transduction is the process by which DNA is transferred from one bacterium to another by a virus. It also refers to the process whereby foreign DNA is introduced into another cell via a viral vector. Transduction does not require cell-to-cell contact , and it is DNAase resistant...
of bacteria by bacteriophages was first described in the same year.
In 1949 John F. Enders, Thomas Weller
Thomas Huckle Weller
Thomas Huckle Weller was an American virologist. He, John Franklin Enders and Frederick Chapman Robbins were awarded a Nobel Prize in Physiology or Medicine in 1954 for showing how to cultivate poliomyelitis viruses in a test tube, using tissue from a monkey.Weller was born and grew up in Ann...
and Frederick Robbins reported that they had been able to grow poliovirus
Poliovirus
Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the family of Picornaviridae.Poliovirus is composed of an RNA genome and a protein capsid. The genome is a single-stranded positive-sense RNA genome that is about 7500 nucleotides long. The viral particle is...
in cultured human embryonal cells, the first significant example of an animal virus grown outside of animals or chicken eggs. This work aided Jonas Salk
Jonas Salk
Jonas Edward Salk was an American medical researcher and virologist, best known for his discovery and development of the first safe and effective polio vaccine. He was born in New York City to parents from Ashkenazi Jewish Russian immigrant families...
in deriving a polio vaccine from killed polio viruses; this vaccine was shown to be effective in 1955.
The first virus that could be crystal
Crystal
A crystal or crystalline solid is a solid material whose constituent atoms, molecules, or ions are arranged in an orderly repeating pattern extending in all three spatial dimensions. The scientific study of crystals and crystal formation is known as crystallography...
ized and whose structure could therefore be elucidated in detail was tobacco mosaic virus
Tobacco mosaic virus
Tobacco mosaic virus is a positive-sense single stranded RNA virus that infects plants, especially tobacco and other members of the family Solanaceae. The infection causes characteristic patterns on the leaves . TMV was the first virus to be discovered...
(TMV), the virus that had been studied earlier by Ivanovski and Beijerink. In 1935, Wendell Stanley
Wendell Meredith Stanley
Wendell Meredith Stanley was an American biochemist, virologist and Nobel laureate.-Biography:Stanley was born in Ridgeville, Indiana, and earned a BS in Chemistry at Earlham College in Richmond, Indiana. He then studied at the University of Illinois, gaining an MS in science in 1927 followed by...
achieved its crystallization for electron microscopy
Electron microscope
An electron microscope is a type of microscope that uses a beam of electrons to illuminate the specimen and produce a magnified image. Electron microscopes have a greater resolving power than a light-powered optical microscope, because electrons have wavelengths about 100,000 times shorter than...
and showed that it remains active even after crystallization. Clear X-ray diffraction pictures of the crystallized virus were obtained by Bernal and Fankuchen in 1941. Based on such pictures, Rosalind Franklin
Rosalind Franklin
Rosalind Elsie Franklin was a British biophysicist and X-ray crystallographer who made critical contributions to the understanding of the fine molecular structures of DNA, RNA, viruses, coal and graphite...
proposed the full structure of the tobacco mosaic virus in 1955. Also in 1955, Heinz Fraenkel-Conrat and Robley Williams showed that purified TMV RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
and its capsid
Capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
(coat) protein can assemble by themselves to form functional viruses, suggesting that this simple mechanism is likely the natural assembly mechanism within the host cell, as Delbrück had proposed earlier.
In 1963, the Hepatitis B virus was discovered by Baruch Blumberg who went on to develop a vaccine against Hepatitis B.
In 1965, Howard Temin described the first retrovirus
Retrovirus
A retrovirus is an RNA virus that is duplicated in a host cell using the reverse transcriptase enzyme to produce DNA from its RNA genome. The DNA is then incorporated into the host's genome by an integrase enzyme. The virus thereafter replicates as part of the host cell's DNA...
: an RNA-virus that was able to insert its genome in the form of DNA into the host's genome. Reverse transcriptase
Reverse transcriptase
In the fields of molecular biology and biochemistry, a reverse transcriptase, also known as RNA-dependent DNA polymerase, is a DNA polymerase enzyme that transcribes single-stranded RNA into single-stranded DNA. It also helps in the formation of a double helix DNA once the RNA has been reverse...
, the key enzyme that retroviruses use to translate their RNA into DNA, was first described in 1970, independently by Howard Temin and David Baltimore
David Baltimore
David Baltimore is an American biologist, university administrator, and Nobel laureate in Physiology or Medicine. He served as president of the California Institute of Technology from 1997 to 2006, and is currently the Robert A. Millikan Professor of Biology at Caltech...
. The first retrovirus infecting human
Human
Humans are the only living species in the Homo genus...
s was identified by Robert Gallo
Robert Gallo
Robert Charles Gallo is an American biomedical researcher. He is best known for his role in the discovery of the Human Immunodeficiency Virus , the infectious agent responsible for the Acquired Immune Deficiency Syndrome , and he has been a major contributor to subsequent HIV research.Gallo is the...
in 1974. Later it was found that reverse transcriptase is not specific to retroviruses; retrotransposon
Retrotransposon
Retrotransposons are genetic elements that can amplify themselves in a genome and are ubiquitous components of the DNA of many eukaryotic organisms. They are a subclass of transposon. They are particularly abundant in plants, where they are often a principal component of nuclear DNA...
s which code for reverse transcriptase are abundant in the genomes of all eukaryotes. About 10-40% of the human genome derives from such retrotransposons.
In 1975 the functioning of oncoviruses was clarified considerably. Until that time, it was thought that these viruses carried certain genes called oncogene
Oncogene
An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels.An oncogene is a gene found in the chromosomes of tumor cells whose activation is associated with the initial and continuing conversion of normal cells into cancer...
s which, when inserted into the host's genome, would cause cancer. Michael Bishop
J. Michael Bishop
-External links:**...
and Harold Varmus showed that the oncogene of Rous sarcoma virus
Rous sarcoma virus
Rous sarcoma virus is a retrovirus and is the first oncovirus to have been described: it causes sarcoma in chickens.As with all retroviruses, it reverse transcribes its RNA genome into cDNA before integration into the host DNA.-History:...
is in fact not specific to the virus but is contained in the genome of healthy animals of many species. The oncovirus can switch this pre-existing benign proto-oncogene on, turning it into a true oncogene that causes cancer.
1976 saw the first recorded outbreak of Ebola hemorrhagic fever, a highly lethal virally transmitted disease.
In 1977, Frederick Sanger
Frederick Sanger
Frederick Sanger, OM, CH, CBE, FRS is an English biochemist and a two-time Nobel laureate in chemistry, the only person to have been so. In 1958 he was awarded a Nobel prize in chemistry "for his work on the structure of proteins, especially that of insulin"...
achieved the first complete sequencing of the genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....
of any organism, the bacteriophage Phi X 174. In the same year, Richard Roberts
Richard J. Roberts
Sir Richard "Rich" John Roberts is a British biochemist and molecular biologist. He was awarded the 1993 Nobel Prize in Physiology or Medicine with Phillip Allen Sharp for the discovery of introns in eukaryotic DNA and the mechanism of gene-splicing.When he was 4, his family moved to Bath. In...
and Phillip Sharp
Phillip Allen Sharp
Phillip Allen Sharp is an American geneticist and molecular biologist who co-discovered RNA splicing. He shared the 1993 Nobel Prize in Physiology or Medicine with Richard J...
independently showed that the genes of adenovirus contain intron
Intron
An intron is any nucleotide sequence within a gene that is removed by RNA splicing to generate the final mature RNA product of a gene. The term intron refers to both the DNA sequence within a gene, and the corresponding sequence in RNA transcripts. Sequences that are joined together in the final...
s and therefore require gene splicing. It was later realized that almost all genes of eukaryotes have introns as well.
A worldwide vaccination campaign led by the UN World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...
resulted in the eradication of smallpox
Smallpox
Smallpox was an infectious disease unique to humans, caused by either of two virus variants, Variola major and Variola minor. The disease is also known by the Latin names Variola or Variola vera, which is a derivative of the Latin varius, meaning "spotted", or varus, meaning "pimple"...
in 1979.
In 1982, Stanley Prusiner discovered prion
Prion
A prion is an infectious agent composed of protein in a misfolded form. This is in contrast to all other known infectious agents which must contain nucleic acids . The word prion, coined in 1982 by Stanley B. Prusiner, is a portmanteau derived from the words protein and infection...
s and showed that they cause scrapie
Scrapie
Scrapie is a fatal, degenerative disease that affects the nervous systems of sheep and goats. It is one of several transmissible spongiform encephalopathies , which are related to bovine spongiform encephalopathy and chronic wasting disease of deer. Like other spongiform encephalopathies, scrapie...
.
The first cases of AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
were reported in 1981, and HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
, the retrovirus causing it, was identified in 1983 by Robert Gallo
Robert Gallo
Robert Charles Gallo is an American biomedical researcher. He is best known for his role in the discovery of the Human Immunodeficiency Virus , the infectious agent responsible for the Acquired Immune Deficiency Syndrome , and he has been a major contributor to subsequent HIV research.Gallo is the...
and Luc Montagnier
Luc Montagnier
Luc Antoine Montagnier is a French virologist and joint recipient with Françoise Barré-Sinoussi and Harald zur Hausen of the 2008 Nobel Prize in Physiology or Medicine, for his discovery of the human immunodeficiency virus...
. Tests detecting HIV infection by detecting the presence of HIV antibody were developed. Subsequent tremendous research efforts turned HIV into the best studied virus. Human Herpes Virus 8
Kaposi's sarcoma-associated herpesvirus
Kaposi's sarcoma-associated herpesvirus is one of seven currently known human cancer viruses, or oncoviruses. It is also the eighth human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses is HHV-8. Like other herpesviruses, its informal name is used...
, the cause of Kaposi's sarcoma
Kaposi's sarcoma
Kaposi's sarcoma is a tumor caused by Human herpesvirus 8 , also known as Kaposi's sarcoma-associated herpesvirus . It was originally described by Moritz Kaposi , a Hungarian dermatologist practicing at the University of Vienna in 1872. It became more widely known as one of the AIDS defining...
which is often seen in AIDS patients, was identified in 1994. Several antiretroviral drug
Antiretroviral drug
Antiretroviral drugs are medications for the treatment of infection by retroviruses, primarily HIV. When several such drugs, typically three or four, are taken in combination, the approach is known as Highly Active Antiretroviral Therapy, or HAART...
s were developed in the late 1990s, decreasing AIDS mortality dramatically in developed countries.
The Hepatitis C virus
Hepatitis C virus
Hepatitis C virus is a small , enveloped, positive-sense single-stranded RNA virus of the family Flaviviridae...
was identified using novel molecular cloning
Molecular cloning
Molecular cloning refers to a set of experimental methods in molecular biology that are used to assemble recombinant DNA molecules and to direct their replication within host organisms...
techniques in 1987, leading to screening tests that dramatically reduced the incidence of post-transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...
.
The first attempts at gene therapy
Gene therapy
Gene therapy is the insertion, alteration, or removal of genes within an individual's cells and biological tissues to treat disease. It is a technique for correcting defective genes that are responsible for disease development...
involving viral vectors began in the early 1980s, when retroviruses were developed that could insert a foreign gene into the host's genome. They contained the foreign gene but did not contain the viral genome and therefore could not reproduce. Tests in mice were followed by tests in human
Human
Humans are the only living species in the Homo genus...
s, beginning in 1989. The first human studies attempted to correct the genetic disease severe combined immunodeficiency
Severe combined immunodeficiency
Severe combined immunodeficiency , is a genetic disorder in which both "arms" of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency...
(SCID), but clinical success was limited. In the period from 1990 to 1995, gene therapy was tried on several other diseases and with different viral vectors, but it became clear that the initially high expectations were overstated. In 1999 a further setback occurred when 18-year-old Jesse Gelsinger
Jesse Gelsinger
Jesse Gelsinger was the first person publicly identified as having died in a clinical trial for gene therapy....
died in a gene therapy trial. He suffered a severe immune response after having received an adenovirus vector. Success in the gene therapy of two cases of X-linked SCID
Severe combined immunodeficiency
Severe combined immunodeficiency , is a genetic disorder in which both "arms" of the adaptive immune system are impaired due to a defect in one of several possible genes. SCID is a severe form of heritable immunodeficiency...
was reported in 2000.
In 2002 it was reported that poliovirus
Poliovirus
Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and member of the family of Picornaviridae.Poliovirus is composed of an RNA genome and a protein capsid. The genome is a single-stranded positive-sense RNA genome that is about 7500 nucleotides long. The viral particle is...
had been synthetically assembled in the laboratory, representing the first synthetic organism. Assembling the 7741-base genome from scratch, starting with the virus's published RNA sequence, took about two years. In 2003 a faster method was shown to assemble the 5386-base genome of the bacteriophage Phi X 174 in 2 weeks.
The giant mimivirus
Mimivirus
Mimivirus is a viral genus containing a single identified species named Acanthamoeba polyphaga mimivirus , or is a group of phylogenetically related large viruses . In colloquial speech, APMV is more commonly referred to as just “mimivirus”...
, in some sense an intermediate between tiny prokaryotes and ordinary viruses, was described in 2003 and sequenced
DNA sequencing
DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....
in 2004.
The strain of Influenza A virus subtype H1N1 that killed up to 50 million people during the Spanish flu
Spanish flu
The 1918 flu pandemic was an influenza pandemic, and the first of the two pandemics involving H1N1 influenza virus . It was an unusually severe and deadly pandemic that spread across the world. Historical and epidemiological data are inadequate to identify the geographic origin...
pandemic in 1918 was reconstructed in 2005. Sequence information was pieced together from preserved tissue samples of flu victims; viable virus was then synthesized from this sequence. The 2009 flu pandemic
2009 flu pandemic
The 2009 flu pandemic was an influenza pandemic, and the second of the two pandemics involving H1N1 influenza virus , albeit in a new version...
involved another strain of Influenza A H1N1, commonly known as "swine flu".
By 1985, Harald zur Hausen
Harald zur Hausen
Harald zur Hausen is a German virologist and professor emeritus. He has done research on cancer of the cervix, where he discovered the role of papilloma viruses, for which he received the Nobel Prize in Physiology or Medicine 2008.-Biography:Zur Hausen was born in Gelsenkirchen, Germany, went to...
had shown that two strains of Human papillomavirus
Human papillomavirus
Human papillomavirus is a member of the papillomavirus family of viruses that is capable of infecting humans. Like all papillomaviruses, HPVs establish productive infections only in keratinocytes of the skin or mucous membranes...
(HPV) cause most cases of cervical cancer
Cervical cancer
Cervical cancer is malignant neoplasm of the cervix uteri or cervical area. One of the most common symptoms is abnormal vaginal bleeding, but in some cases there may be no obvious symptoms until the cancer is in its advanced stages...
. Two vaccines protecting against these strains were released in 2006.
In 2006 and 2007 it was reported that introducing a small number of specific transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
genes into normal skin cells of mice or human
Human
Humans are the only living species in the Homo genus...
s can turn these cells into pluripotent stem cell
Stem cell
This article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
s, known as Induced Pluripotent Stem Cell
Induced pluripotent stem cell
Induced pluripotent stem cells, commonly abbreviated as iPS cells or iPSCs are a type of pluripotent stem cell artificially derived from a non-pluripotent cell, typically an adult somatic cell, by inducing a "forced" expression of specific genes....
s. The technique uses modified retroviruses to transform the cells; this is a potential problem for human therapy since these viruses integrate their genes at a random location in the host's genome, which can interrupt other genes and potentially causes cancer.
In 2008, Sputnik virophage
Sputnik virophage
Sputnik virophage is a subviral agent that reproduces in amoeba cells that are already infected by a certain helper virus; Sputnik uses the helper virus's machinery for reproduction and inhibits replication of the helper virus.Viruses like Sputnik that depend on co-infection of the host cell by...
was described, the first known virophage: it uses the machinery of a helper virus to reproduce and inhibits reproduction of that helper virus. Sputnik reproduces in amoeba infected by mamavirus
Mamavirus
Mamavirus is one of the most complex viruses discovered. It is a virus belonging to the family mimiviridae, which includes mimivirus, mamavirus, and marseillevirus The mimiviridae also belong to the family of the nucleocytoplasmic large DNA viruses , which includes the Poxviridae, the...
, a relative of the mimivirus mentioned above and the largest known virus to date.
See also
- Introduction to virusesIntroduction to virusesA virus is a biological agent that reproduces inside the cells of living hosts. When infected by a virus, a host cell is forced to produce many thousands of identical copies of the original virus, at an extraordinary rate. Unlike most living things, viruses do not have cells that divide; new...
- Virus
- Virus classificationVirus classificationVirus classification is the process of naming viruses and placing them into a taxonomic system. Similar to the classification systems used for cellular organisms, virus classification is the subject of ongoing debate and proposals. This is mainly due to the pseudo-living nature of viruses, which...
- List of viruses
- Clinical virologyClinical virologyClinical or medical virology is a branch of medicine which consists in isolating and/or in characterising one or several viruses responsible for some human pathologies by various direct or indirect techniques...
- Animal virologyAnimal virologyThe study of animal viruses is important from a veterinary viewpoint and many of these viruses cause diseases that are economically devastating. Many animal viruses are also important from a human medical perspective...
- :Category:Viral diseases
- List of viral diseases
- Important publications in virology
- Wikipedia:WikiProject Viruses
External links and sources
- ICTV: International Committee on Taxonomy of Viruses - searchable virus taxonomy, updated versions in 2007 and 2008. Explanations of the virus species concept and viral taxonomy.
- David Sander: All the Virology on the WWW - collection of links, pictures, lecture notes. Many of the links on this site are broken and it does not appear to be being maintained.
- Online lectures in virology University of South Carolina
- MicrobiologyBytes: Origins of Virology
- MicrobiologyBytes: The Virology Time Machine
- Timeline of the history of virology, from the Washington University in St. LouisWashington University in St. LouisWashington University in St. Louis is a private research university located in suburban St. Louis, Missouri. Founded in 1853, and named for George Washington, the university has students and faculty from all fifty U.S. states and more than 110 nations...
. - Wong's Virology.
- Vaccine Research Center (VRC) - Information concerning vaccine research studies
- This Week in Virology Podcast by Vincent RacanielloVincent RacanielloVincent R. Racaniello is a Higgins Professor in the Department of Microbiology and Immunology at Columbia University’s College of Physicians and Surgeons...
http://www.twiv.tv/