Rubella virus
Encyclopedia
- This page is for the virus. For the disease, see RubellaRubellaRubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is...
.
Rubella virus is the pathogenic agent of the disease Rubella
Rubella
Rubella, commonly known as German measles, is a disease caused by the rubella virus. The name "rubella" is derived from the Latin, meaning little red. Rubella is also known as German measles because the disease was first described by German physicians in the mid-eighteenth century. This disease is...
, and is the cause of congenital rubella syndrome
Congenital rubella syndrome
Congenital rubella syndrome can occur in a developing fetus of a pregnant woman who has contracted rubella during her first trimester. If infection occurs 0–28 days before conception, there is a 43% chance the infant will be affected. If the infection occurs 0–12 weeks after conception, there is a...
when infection occurs during the first weeks of lunacy
Lunacy
Lunacy may refer to:* Lunacy, the condition suffered by a lunatic, now used only informally* Lunacy , a 2005 Jan Švankmajer's film* Lunacy , a video game for Sega Saturn* Luna Sea, a Japanese rock band originally named Lunacy...
.
Humans are the only known host of this virus.
Rubella virus is the only member of the genus of Rubivirus and belongs to the family of Togaviridae
Togaviridae
The Togaviridae are a family of viruses, including the following genera:* Genus Alphavirus; type species: Sindbis virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Ross River virus, O'nyong'nyong virus, Chikungunya* Genus Rubivirus;...
, whose members commonly have a genome of single-stranded RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
of positive polarity
Sense (molecular biology)
In molecular biology and genetics, sense is a concept used to compare the polarity of nucleic acid molecules, such as DNA or RNA, to other nucleic acid molecules...
which is enclosed by an icosahedral
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....
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...
.
The molecular basis for the causation of congenital rubella syndrome are not yet completely clear, but in vitro studies with cell lines showed that Rubella virus has an apoptotic
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...
effect on certain cell types. There is evidence for a p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...
-dependent mechanism.
Structure
The spherical virus particles (virions) of Togaviridae have a diameter of 50 to 70 nm and are covered by a lipid membrane (viral envelopeViral 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...
), derived from the host cell membrane. There are prominent "spikes" (projections) of 6 nm composed of the viral envelope proteins E1 and E2 embedded in the membrane.
Inside the lipid envelope is a capsid of 40 nm in diameter.
The E1 glycoprotein is considered immunodominant in the humoral response induced against the structural proteins and contains both neutralizing and hemagglutinating determinants.
Genome
The genome has 9,762 nucleotides and encodes 2 nonstructural polypeptides (p150 and p90) within its 5′-terminal two-thirds and 3 structural polypeptides (C, E2, and E1) within its 3′-terminal one-third.Both envelope proteins E1 and E2 are glycosylated
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
.
There are three sites that are highly conserved in togviruses: a stem-and-loop structure at the 5' end of the genome, a 51-nucleotide conserved sequence near the 5' end of the genome and a 20-nucleotide conserved sequence at the subgenomic RNA start site. Homologous sequenes are present in the rubella genome.
The genome encodes several non-coding RNA
Non-coding RNA
A non-coding RNA is a functional RNA molecule that is not translated into a protein. Less-frequently used synonyms are non-protein-coding RNA , non-messenger RNA and functional RNA . The term small RNA is often used for short bacterial ncRNAs...
structures; among them is the rubella virus 3' cis-acting element
Rubella virus 3' cis-acting element
The Rubella virus 3' cis-acting element RNA family represents a cis-acting element found at the 3' UTR in the rubella virus. This family contains three conserved step loop structures. Calreticulin , which is known to bind calcium in most eukaryotic cells, is able to specifically bind to the first...
, which contains multiple stem-loop
Stem-loop
Stem-loop intramolecular base pairing is a pattern that can occur in single-stranded DNA or, more commonly, in RNA. The structure is also known as a hairpin or hairpin loop. It occurs when two regions of the same strand, usually complementary in nucleotide sequence when read in opposite directions,...
s, one of which has been found to be essential for viral replication.
The only significant region of homology between rubella and the alphaviruses is located at the NH2 terminus of non structural protein 3. This sequence has helicase
Helicase
Helicases are a class of enzymes vital to all living organisms. They are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separating two annealed nucleic acid strands using energy derived from ATP hydrolysis.-Function:Many cellular processes Helicases are a...
and replicase activity. In the rubella genome these occur in the opposite orientation to that found in the alphaviruses indicating that a genome rearrangment has occurred.
Replication
The virus attach to the cell surface via specific receptors and are taken up by an endosomeEndosome
In biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the endocytic membrane transport pathway from the plasma membrane to the lysosome. Molecules internalized from the plasma membrane can follow this pathway all the way to lysosomes for...
being formed. At the neutral pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
outside of the cell the E2 envelope protein covers the E1 protein. The dropping pH inside the endosome frees the outer domain of E1 and causes the fusion of the viral envelope with the endosomal membrane. Thus, the capsid reaches the cytosol
Cytosol
The cytosol or intracellular fluid is the liquid found inside cells, that is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondrion into compartments....
, decays and releases the genome
The (+)ssRNA (positive
Sense (molecular biology)
In molecular biology and genetics, sense is a concept used to compare the polarity of nucleic acid molecules, such as DNA or RNA, to other nucleic acid molecules...
, single-stranded RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
) at first only acts as a template for the translation of the non-structural proteins, which are synthesized as a large polyprotein and are then cut into single proteins. The sequences for the structural proteins are first replicated by the viral RNA polymerase
RNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...
(Replicase) via a complementary (-)ssRNA as a template and translated as a separate short mRNA. This short subgenomic RNA is additionally packed in a virion.
Translation of the structural proteins produces a large polypeptide (110 Dalton
KDA
KDA may refer to:* Karachi Development Authority* Kongsberg Defence & Aerospace* Kotelawala Defence Academy* Kramer Design Associates* Lithium diisopropylamide, KDA is the potassium analogue of lithium diisopropylamideOr kDa may refer to:...
). This is then endoproteolytically
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
cut into E1, E2 and the capsid protein. E1 and E2 are type I transmembrane protein
Transmembrane protein
A transmembrane protein is a protein that goes from one side of a membrane through to the other side of the membrane. Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as...
s which are transported into the endoplasmatic reticulum (ER) with the help of an N-terminal signal sequence. From the ER the heterodimeric E1·E2-complex reaches the Golgi apparatus
Golgi apparatus
The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....
, where the budding of new virions occurs (unlike alpha viruses, where budding occurs at the plasma membrane.
The capsid proteins on the other hand stay in the cytoplasm and interact with the genomic RNA, together forming the capsid.
Capsid protein
The capsid protein (CP) has different functions. Its main tasks are the formation of homooligomeres to form the capsid, and the binding of the genomic RNA. Further is it responsible for the aggregation of RNA in the capsid, it interacts with the membrane proteins E1 and E2 and binds the human host-protein p32 which is important for replication of the virus in the host.As opposed to alpha viruses the capsid does not undergo autoprotolysis, rather is it cut off from the rest of the polyprotein by the signal-peptidase. Production of the capsid happens at the surface of intracellular membranes simultaneously with the budding of the virus.
Epidemiology
On the basis of differences in the sequence of the E1 protein two genotypes have been described that differing by 8 - 10%. These have been subdivided into 13 recognised genotypes - 1a, 1B, 1C, 1D, 1E, 1F, 1G, 1h, 1i, 1j, 2A, 2B and 2C.For typing the WHO recommends a minimum window that includes nucleotides 8731 to 9469.
Genotypes 1a, 1E, 1F, 2A and 2B have been isolated in China
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...
.
Genotype 1j has only been isolated from Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
and the Philippines
Philippines
The Philippines , officially known as the Republic of the Philippines , is a country in Southeast Asia in the western Pacific Ocean. To its north across the Luzon Strait lies Taiwan. West across the South China Sea sits Vietnam...
.
Genotype 1E is found in Africa
Africa
Africa is the world's second largest and second most populous continent, after Asia. At about 30.2 million km² including adjacent islands, it covers 6% of the Earth's total surface area and 20.4% of the total land area...
, the Americas
Americas
The Americas, or America , are lands in the Western hemisphere, also known as the New World. In English, the plural form the Americas is often used to refer to the landmasses of North America and South America with their associated islands and regions, while the singular form America is primarily...
, Asia
Asia
Asia is the world's largest and most populous continent, located primarily in the eastern and northern hemispheres. It covers 8.7% of the Earth's total surface area and with approximately 3.879 billion people, it hosts 60% of the world's current human population...
and Europe
Europe
Europe is, by convention, one of the world's seven continents. Comprising the westernmost peninsula of Eurasia, Europe is generally 'divided' from Asia to its east by the watershed divides of the Ural and Caucasus Mountains, the Ural River, the Caspian and Black Seas, and the waterways connecting...
.
Genotype 1G has been isolated in Belarus
Belarus
Belarus , officially the Republic of Belarus, is a landlocked country in Eastern Europe, bordered clockwise by Russia to the northeast, Ukraine to the south, Poland to the west, and Lithuania and Latvia to the northwest. Its capital is Minsk; other major cities include Brest, Grodno , Gomel ,...
, Cote d'Ivoire
Côte d'Ivoire
The Republic of Côte d'Ivoire or Ivory Coast is a country in West Africa. It has an area of , and borders the countries Liberia, Guinea, Mali, Burkina Faso and Ghana; its southern boundary is along the Gulf of Guinea. The country's population was 15,366,672 in 1998 and was estimated to be...
and Uganda
Uganda
Uganda , officially the Republic of Uganda, is a landlocked country in East Africa. Uganda is also known as the "Pearl of Africa". It is bordered on the east by Kenya, on the north by South Sudan, on the west by the Democratic Republic of the Congo, on the southwest by Rwanda, and on the south by...
.
Genotype 1C is endemic only in Central and South America.
Genotype 2B has been isolated in South Africa
South Africa
The Republic of South Africa is a country in southern Africa. Located at the southern tip of Africa, it is divided into nine provinces, with of coastline on the Atlantic and Indian oceans...
.
Genotype 2C has been isolated in Russia
Russia
Russia or , officially known as both Russia and the Russian Federation , is a country in northern Eurasia. It is a federal semi-presidential republic, comprising 83 federal subjects...
.
Literature
- David M. Knipe, Peter M. Howley et al. (eds.): Fields´ Virology 4. Auflage, Philadelphia 2001
- C.M. Fauquet, M.A. Mayo et al.: Eighth Report of the International Committee on Taxonomy of Viruses, London San Diego 2005