Alphavirus

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Alphavirus
Structure and genome of an alphavirus
A computer-generated model of the surface of an Alphavirus derived by heterodimers of the virion surface Glycoproteins E1 and E2 . These spikes are used by the virus to attach to susceptible animal cells
Virus classification
(unranked):	Virus
Realm:	Riboviria
Kingdom:	Orthornavirae
Phylum:	Kitrinoviricota
Class:	Alsuviricetes
Order:	Martellivirales
Family:	Togaviridae
Genus:	Alphavirus
Species
Aura virus Barmah Forest virus Bebaru virus Caaingua virus Cabassou virus Chikungunya virus Eastern equine encephalitis virus Eilat virus Everglades virus Fort Morgan virus Getah virus Highlands J virus Madariaga virus Mayaro virus Middelburg virus Mosso das Pedras virus Mucambo virus Ndumu virus O'nyong'nyong virus Pixuna virus Rio Negro virus Ross River virus Salmon pancreas disease virus Semliki Forest virus Sindbis virus Southern elephant seal virus Tonate virus Trocara virus Una virus Venezuelan equine encephalitis virus Western equine encephalitis virus Whataroa virus

Alphavirus is a genus of

Genome

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Alpha_E1_glycop
TCDB		1.G
OPM superfamily	109
OPM protein	1rer
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Alpha_E2_glycop
TCDB		1.G
OPM superfamily	109
OPM protein	2yew
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Alpha_E3_glycop
Identifiers
Symbol	Alpha_E3_glycop
TCDB	1.G
OPM superfamily	109
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

The alphaviruses are small, spherical, enveloped viruses with a genome of a single strand of positive-sense RNA. The total genome length ranges between 11,000 and 12,000 nucleotides, and has a

poly-A tail

. The four non-structural protein genes are encoded in the 5′ two-thirds of the genome, while the three structural proteins are translated from a subgenomic mRNA colinear with the 3′ one-third of the genome.

There are two

membrane fusion

.

Structural proteins

The

Four nonstructural proteins (nsP1–4) which are produced as a single polyprotein constitute the virus' replication machinery.[5] The processing of the polyprotein occurs in a highly regulated manner, with cleavage at the P2/3 junction influencing RNA template use during genome replication. This site is located at the base of a narrow cleft and is not readily accessible. Before cleavage, nsP3 creates a ring structure that encircles nsP2. These two proteins have an extensive interface.

Mutations in nsP2 that produce noncytopathic viruses or a temperature sensitive phenotypes cluster at the P2/P3 interface region. P3 mutations opposite the location of the nsP2 noncytopathic mutations prevent efficient cleavage of P2/3. This in turn affects RNA infectivity altering viral RNA production levels.

Virology

The virus has a 60–70

The nucleocapsid, 40 nanometers in diameter, contains 240 copies of the capsid protein and has a T = 4 icosahedral symmetry. The E1 and E2 viral glycoproteins are embedded in the lipid bilayer. Single E1 and E2 molecules associate to form heterodimers. The E1–E2 heterodimers form one-to-one contacts between the E2 protein and the nucleocapsid monomers. The E1 and E2 proteins mediate contact between the virus and the host cell.

Several receptors have been identified. These include prohibitin, phosphatidylserine, glycosaminoglycans and ATP synthase β subunit (ref needed).

Replication occurs within the cytoplasm, specifically in areas termed "spherules" separated by plasma membrane invaginations from the rest. Each complex occupies one such area of about 50-nm in inner diameter.^[6]

Virions mature by budding through the plasma membrane, where virus-encoded surface glycoproteins E2 and E1 are assimilated. These two glycoproteins are the targets of numerous serologic reactions and tests including neutralization and hemagglutination inhibition. The alphaviruses show various degrees of antigenic cross-reactivity in these reactions and this forms the basis for the seven antigenic complexes, 32 species and many subtypes and varieties. The E2 protein is the site of most neutralizing epitopes, while the E1 protein contains more conserved, cross-reactive epitopes.

Evolution

A study of this taxon suggests that this group of viruses had a marine origin—specifically the Southern Ocean—and that they have subsequently spread to both the Old and New World.^[7]

There are three subgroups in this genus: the Semliki Forest virus subgroup (Semliki Forest, O'nyong-nyong and Ross River viruses); the eastern equine encephalitis virus subgroup (eastern equine encephalitis and Venezuelan equine encephalitis viruses) and the Sindbis virus subgroup.^[8] Sindbis virus, geographically restricted to the Old World, is more closely related to the eastern equine encephalitis subgroup, which are New World viruses, than it is to the Semliki Forest virus subgroup which is also found in the Old World.

Taxonomy

The following species are assigned to the genus:^[9]

The seven complexes are:

Barmah Forest virus complex

Barmah Forest virus

Eastern equine encephalitis complex

Eastern equine encephalitis virus

(seven antigenic types)

Middelburg virus complex

Middelburg virus

Ndumu virus complex

Ndumu virus

Semliki Forest virus complex

Bebaru virus

Chikungunya virus

Getah virus

Mayaro virus

Subtype: Una virus

O'nyong'nyong virus

Subtype: Igbo-Ora virus

Ross River virus

Subtype:

Sagiyama virus

Semliki Forest virus

Subtype: Me Tri virus

Venezuelan equine encephalitis complex

Cabassou virus

Everglades virus

Mosso das Pedras virus

Mucambo virus

Paramana virus

Pixuna virus

Rio Negro virus

Trocara virus

Subtype: Bijou Bridge virus

Venezuelan equine encephalitis virus

Western equine encephalitis complex

Aura virus

Babanki virus

Kyzylagach virus

Sindbis virus

Ockelbo virus

Whataroa virus

Recombinants within this complex

Buggy Creek virus

Fort Morgan virus

Highlands J virus

Western equine encephalitis virus

Unclassified

Eilat virus

Mwinilunga alphavirus

Salmonid Alphavirus

Southern elephant seal virus

Tonate

virus

Caaingua virus^[10]

Notes

Barmah Forest virus is related to the Semliki Forest virus. Middelburg virus, although classified as a separate complex, may be a member of the Semliki Forest virus group.

It seems likely that the genus evolved in the Old World from an insect-borne plant virus.^[11]

Sindbis virus may have originated in South America.^[12] The equine encephalitis viruses and the Sindbis virus are related.

The Old World and New World viruses appears to have diverged between 2000 and 3000 years ago.^[13] Divergence between the Venezuelan equine encephalitis virus and the eastern equine virus appears to have been ~1400 years ago.^[14]

The fish infecting clade appears to be basal to the other species.

The southern elephant seal virus appears to be related to the Sinbis clade.

Pathogenesis and immune response

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There are many alphaviruses distributed around the world with the ability to cause human disease. Infectious

Terrestrial alphavirus infections are spread by insect vectors such as mosquitoes. Once a human is bitten by the infected mosquito, the virus can gain entry into the bloodstream, causing viremia. The alphavirus can also get into the CNS where it is able to grow and multiply within the neurones. This can lead to encephalitis, which can be fatal.

When an individual is infected with this particular virus, its immune system can play a role in clearing away the virus particles. Alphaviruses are able to cause the production of

Diagnosis, prevention, and control

Diagnoses is based on clinical samples from which the virus can be easily isolated and identified. There are no alphavirus vaccines currently available. Vector control with repellents, protective clothing, breeding site destruction, and spraying are the preventive measures of choice.^{[citation needed]}

Research

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Alphaviruses are of interest to

Initially, the Togaviridae family included what are now called the Flaviviruses, within the Alphavirus genus. The flaviviruses were formed into their own family when sufficient differences with the alphaviruses were noted due to the development of sequencing.^[15] Rubella virus was formerly included in the family Togaviridae in its own genus Rubivirus, but is now classified in its own family Matonaviridae.^[16] Alphavirus is now the sole genus in the family.

• 1930 – Western equine encephalitis virus is first isolated in the United States (the first alphavirus ever isolated)
• 1933 –
  Eastern equine encephalitis virus
  is first isolated in the United States.
• 1938 – Venezuelan equine encephalitis is isolated.
• 1941 – Western equine encephalitis epidemic is seen in the United States. It affects 300,000 horses and 3,336 humans.
• 1941 –
  cataracts following a rubella outbreak. This and other defects are then categorized under the congenital rubella syndrome
  .
• 1942 –
  Semliki Forest virus is isolated in Buliyama, Bwamba County, Uganda
  .
• 1952 – Sindbis virus is isolated in the Sindbis health district, 40 mi (64 km) north of Cairo, Egypt.
• 1959 – Ross River virus is isolated from Aedes vigilax mosquitoes (now known as Ochlerotatus vigilax)^[17] which were trapped at the Ross River in Australia.
• 1963 – Ross River virus, which causes
  epidemic polyarthritis (mostly seen in Australia), is isolated by Doherty and colleagues.^[18]
• 1971 – Last epidemic of Venezuelan equine encephalitis is seen in horses in southern Texas.^[19]
• 1986 –
  Barmah Forest virus is identified as causing human disease in Australia.^[20]
• 2001 – Scientists solved the
  Semliki Forest virus
  .
• 2005–2006 – Large epidemic of the
  chikungunya virus on the island of La Réunion and the surrounding islands in the Indian Ocean^[21]
• 2006 – Major epidemic of the chikungunya virus in India with over 1.5 million cases reported[22]

See also

• Alphavirus infection

Sources