Virus latency
Encyclopedia
Virus latency is the ability of a pathogen
ic virus
to lie dormant
(latent
) within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic
viral infection. A latent infection is a phase in certain viruses' life cycles in which after initial infection, virus production ceases. However, the virus genome is not fully eradicated. The result of this is that the virus can reactivate and begin producing large amounts of viral progeny without the host being infected by new outside virus, denoted as the lytic part of the viral life cycle, and stays within the host indefinitely.
Virus latency is not to be confused with clinical latency during the incubation period
when a virus is not dormant.
or nucleus
as distinct objects, both as linear or lariat
structures. Episomal latency is more vulnerable to ribozymes or host foreign gene degradation than provirus latency.
One example is Herpes Virus family, Herpesviridae
, all of which establish latent infection. Herpes virus include Chicken-pox virus
and Herpes simplex virus
es (HSV-1, HSV-2), all of which establish episomal latency in neurons and leave linear genetic material floating in the cytoplasm. The Gammaherpesvirinae
subfamily is associated with episomal latency established in cells of the immune system
, such as B-cells in the case of Epstein-Barr Virus
.
Advantages of episomal latency include the fact that the virus may not need to enter the nucleus, and hence may avoid ND10 domains from activating interferon
via that pathway.
Disadvantages include more exposure to cellular defenses, leading to possible degradation of viral gene via cellular enzymes.
integrates into the host genome, effectively become a provirus
. This requires that the viral gene get into the nucleus and insert itself into the host genome, the family of which exemplifies this behavior being the Retrovirus
es. For example, the retrovirus HIV
enters the nucleus and inserts its gene between Long terminal repeat
s using integrase
and remains within the hosts own gene.
Advantages include automatic host cell division results in replication of the viruses gene, and the fact that it is near impossible to remove an integrated provirus from an infected cell without killing the cell
.
Disadvantages include the need to enter the nucleus (and the need for packaging proteins that will allow for that) and increased difficulty in maintaining the latency.
. Certain viral gene products (RNA transcripts such as non-coding RNAs and proteins) may also inhibit apoptosis
or induce cell growth and division
to allow more copies of the infected cell to be produced.
An example of such a gene product is the Latency Associated Transcripts (LAT)
in Herpes simplex virus
, which interfere with apoptosis
by downregulating a number of host factors, including Major Histocompatibility Complex
(MHC) and inhibiting the apoptotic pathway.
A certain type of latency could be ascribed to the endogenous retrovirus
es. These viruses have incorporated into the human genome in the distant past, and are now passed through reproduction. Generally these types of viruses have become highly evolved, and have lost the expression of many gene products. Some of the proteins expressed by these viruses have co-evolved with host cells to play important roles in normal processes.
nor causes any pathologies or symptom
s, the virus is still able to reactivate via external activators (i.e. sunlight, stress) to cause an acute
infection. In the case of Herpes simplex virus
, which generally infects an individual for life, a serotype of the virus reactivates occasionally to cause cold sores. Although the sores are quickly resolved by the immune system, they may be a minor annoyance from time to time. In the case of varicella zoster virus
, after an initial acute infection (chickenpox
) the virus lies dormant until reactivated as herpes zoster
.
More serious ramifications of a latent infection could be the possibility of transforming the cell, and forcing the cell into uncontrolled cell division
. This is a result of the random insertion of the viral genome into the hosts own gene and suppression of host cellular growth factors for the benefit of the virus. A famous event of this actually happening with gene therapy
through the use of retroviral vectors is the Necker Hospital in Paris
, where 20 young boys received treatment for a genetic disorder, after which 5 developed leukemia
-like syndromes .
This is also seen with infections of the human papilloma virus in which persistent
infection may lead to cervical cancer
as a result of cellular transformation.
In the field of HIV
research, proviral latency in specific long-lived cell types is the basis for the concept of one or more viral reservoirs, referring to locations (cell types or tissues) characterized by persistence of latent virus. Specifically, the presence of replication-competent HIV in resting CD4-positive T cells, allows this virus to persist for years without evolving despite prolonged exposure to antiretroviral drugs. This latent reservoir of HIV may explain the inability of antiretroviral treatment to cure HIV infection.
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
ic virus
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...
to lie dormant
Dormancy
Dormancy is a period in an organism's life cycle when growth, development, and physical activity are temporarily stopped. This minimizes metabolic activity and therefore helps an organism to conserve energy. Dormancy tends to be closely associated with environmental conditions...
(latent
Latency
Latency or latent may refer to:*Latency period , the time between exposure to a pathogen, chemical or radiation, and when symptoms first become apparent...
) within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic
Chronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
viral infection. A latent infection is a phase in certain viruses' life cycles in which after initial infection, virus production ceases. However, the virus genome is not fully eradicated. The result of this is that the virus can reactivate and begin producing large amounts of viral progeny without the host being infected by new outside virus, denoted as the lytic part of the viral life cycle, and stays within the host indefinitely.
Virus latency is not to be confused with clinical latency during the incubation period
Incubation period
Incubation period is the time elapsed between exposure to a pathogenic organism, a chemical or radiation, and when symptoms and signs are first apparent...
when a virus is not dormant.
Episomal latency
Episomal latency refers to the use of genetic episomes during latency. In this type, viral genes are floating in the cytoplasmCytoplasm
The cytoplasm is a small gel-like substance residing between the cell membrane holding all the cell's internal sub-structures , except for the nucleus. All the contents of the cells of prokaryote organisms are contained within the cytoplasm...
or 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...
as distinct objects, both as linear or lariat
Lariat
Lariat can refer to:*A rope in the form of a lasso*Lariat chain, a science demonstration*A professional wrestling move, a variation of a clothesline*A genetic structure in Splicing *Double Lariat, a popular song sung by Luka Megurine...
structures. Episomal latency is more vulnerable to ribozymes or host foreign gene degradation than provirus latency.
One example is Herpes Virus family, Herpesviridae
Herpesviridae
The Herpesviridae are a large family of DNA viruses that cause diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word herpein , referring to the latent, recurring infections typical of this group of viruses...
, all of which establish latent infection. Herpes virus include Chicken-pox virus
Varicella zoster virus
Varicella zoster virus is one of eight herpes viruses known to infect humans . It commonly causes chicken-pox in children and Herpes zoster in adults and rarely in children.-Nomenclature:...
and Herpes simplex virus
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...
es (HSV-1, HSV-2), all of which establish episomal latency in neurons and leave linear genetic material floating in the cytoplasm. The Gammaherpesvirinae
Gammaherpesvirinae
Gammaherpesvirinae is a subfamily of Herpesviridae distinguished by reproducing at a more variable rate than other subfamilies of Herpesviridae...
subfamily is associated with episomal latency established in cells of 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...
, such as B-cells in the case of Epstein-Barr Virus
Epstein-Barr virus
The Epstein–Barr virus , also called human herpesvirus 4 , is a virus of the herpes family and is one of the most common viruses in humans. It is best known as the cause of infectious mononucleosis...
.
Advantages of episomal latency include the fact that the virus may not need to enter the nucleus, and hence may avoid ND10 domains from activating 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...
via that pathway.
Disadvantages include more exposure to cellular defenses, leading to possible degradation of viral gene via cellular enzymes.
Proviral latency
Proviral latency begins when the virus genomeGenome
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....
integrates into the host genome, effectively become a provirus
Provirus
A provirus is a virus genome that is integrated into the DNA of a host cell.This state can be a stage of virus replication, or a state that persists over longer periods of time as either inactive viral infections or an endogenous retrovirus. In inactive viral infections the virus will not replicate...
. This requires that the viral gene get into the nucleus and insert itself into the host genome, the family of which exemplifies this behavior being the 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...
es. For example, the retrovirus 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...
enters the nucleus and inserts its gene between Long terminal repeat
Long terminal repeat
Long terminal repeats are sequences of DNA that repeat hundreds or thousands of times. They are found in retroviral DNA and in retrotransposons, flanking functional genes...
s using integrase
Integrase
Retroviral integrase is an enzyme produced by a retrovirus that enables its genetic material to be integrated into the DNA of the infected cell...
and remains within the hosts own gene.
Advantages include automatic host cell division results in replication of the viruses gene, and the fact that it is near impossible to remove an integrated provirus from an infected cell without killing the cell
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....
.
Disadvantages include the need to enter the nucleus (and the need for packaging proteins that will allow for that) and increased difficulty in maintaining the latency.
Maintaining latency
Both proviral and episomal latency may require maintenance for continued infection and fidelity of viral genes. Latency is generally maintained by viral genes expressed primarily during latency. Expression of these latency-associated genes may function to keep the viral genome from being digested by cellular ribozymes or being found out by the immune systemImmune 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...
. Certain viral gene products (RNA transcripts such as non-coding RNAs and proteins) may also inhibit apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
or induce cell growth and division
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...
to allow more copies of the infected cell to be produced.
An example of such a gene product is the Latency Associated Transcripts (LAT)
HHV Latency Associated Transcript
HHV Latency Associated Transcript is a length of RNA which accumulates in cells hosting long-term, or latent, Human Herpes Virus infections. The LAT RNA is produced by genetic transcription from a certain region of the viral DNA...
in Herpes simplex virus
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...
, which interfere with apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
by downregulating a number of host factors, including Major Histocompatibility Complex
Major histocompatibility complex
Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
(MHC) and inhibiting the apoptotic pathway.
A certain type of latency could be ascribed to the endogenous retrovirus
Endogenous retrovirus
Endogenous retroviruses are sequences in the genome thought to be derived from ancient viral infections of germ cells in humans, mammals and other vertebrates; as such their proviruses are passed on to the next generation and now remain in the genome....
es. These viruses have incorporated into the human genome in the distant past, and are now passed through reproduction. Generally these types of viruses have become highly evolved, and have lost the expression of many gene products. Some of the proteins expressed by these viruses have co-evolved with host cells to play important roles in normal processes.
Ramifications
While viral latency exhibits no active viral sheddingViral shedding
Viral shedding refers to the successful reproduction, expulsion, and host-cell infection caused by virus progeny. Once replication has been completed and the host cell is exhausted of all resources in making viral progeny, the viruses may begin to leave the cell by several methods.The term is used...
nor causes any pathologies or symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...
s, the virus is still able to reactivate via external activators (i.e. sunlight, stress) to cause an acute
Acute (medicine)
In medicine, an acute disease is a disease with either or both of:# a rapid onset, as in acute infection# a short course ....
infection. In the case of Herpes simplex virus
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...
, which generally infects an individual for life, a serotype of the virus reactivates occasionally to cause cold sores. Although the sores are quickly resolved by the immune system, they may be a minor annoyance from time to time. In the case of varicella zoster virus
Varicella zoster virus
Varicella zoster virus is one of eight herpes viruses known to infect humans . It commonly causes chicken-pox in children and Herpes zoster in adults and rarely in children.-Nomenclature:...
, after an initial acute infection (chickenpox
Chickenpox
Chickenpox or chicken pox is a highly contagious illness caused by primary infection with varicella zoster virus . It usually starts with vesicular skin rash mainly on the body and head rather than at the periphery and becomes itchy, raw pockmarks, which mostly heal without scarring...
) the virus lies dormant until reactivated as herpes zoster
Herpes zoster
Herpes zoster , commonly known as shingles and also known as zona, is a viral disease characterized by a painful skin rash with blisters in a limited area on one side of the body, often in a stripe...
.
More serious ramifications of a latent infection could be the possibility of transforming the cell, and forcing the cell into uncontrolled cell division
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...
. This is a result of the random insertion of the viral genome into the hosts own gene and suppression of host cellular growth factors for the benefit of the virus. A famous event of this actually happening with 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...
through the use of retroviral vectors is the Necker Hospital in Paris
Paris
Paris is the capital and largest city in France, situated on the river Seine, in northern France, at the heart of the Île-de-France region...
, where 20 young boys received treatment for a genetic disorder, after which 5 developed leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...
-like syndromes .
This is also seen with infections of the human papilloma virus in which persistent
Chronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...
infection may lead to 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...
as a result of cellular transformation.
In the field of 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...
research, proviral latency in specific long-lived cell types is the basis for the concept of one or more viral reservoirs, referring to locations (cell types or tissues) characterized by persistence of latent virus. Specifically, the presence of replication-competent HIV in resting CD4-positive T cells, allows this virus to persist for years without evolving despite prolonged exposure to antiretroviral drugs. This latent reservoir of HIV may explain the inability of antiretroviral treatment to cure HIV infection.