Togaviridae

Group: ssRNA(+)

[1]

The Togaviridae family belongs to group IV of the Baltimore classification of viruses. The genome is linear, nonsegmented, single-stranded, positive-sense RNA that is 10,000–12,000 nucleotides long. The 5'-terminus carries a methylated nucleotide cap and the 3'-terminus has a polyadenylated tail, therefore resembling cellular mRNA. The virus is enveloped and forms spherical particles (65–70 nm diameter), the capsid within is icosahedral, constructed of 240 monomers, having a triangulation number of 4.[1][3][4][5]

Entry into the host cell is achieved by attachment of the viral E glycoprotein to host receptors, which mediates clathrin-mediated endocytosis.[1][3] The receptors for binding are unknown, but the tropism is varied and the glycoprotein petal-like spikes are known to act as attachment proteins. After virus attachment and entry into the cell, gene expression and replication takes place within the cytoplasm.[4][5]

Replication follows the positive-stranded RNA virus replication model. Positive-stranded RNA virus transcription is the method of transcription. Translation takes place by viral initiation, and suppression of termination. The vector for the Togaviridae is primarily the mosquito, where replication of the virus occurs. The family Togaviridae is classified into Old World and New World viruses based on geographical distribution, although a few transoceanic crossings likely have occurred.[4][5] Human, mammals, marsupials, birds, and mosquitoes serve as the natural host. Transmission routes are zoonosis, bite, and respiratory.[1][3]

The nonstructural proteins are encoded at the 5' end, formed during the first of two characteristic rounds of translation. These proteins are originally translated as a polyprotein, which consequently undergo self cleavage, forming four nonstructural proteins responsible for gene expression and replication. The formation of P1234 occurs due to a stop codon read-through, which has a 10% to 20% chance of occurrence.[6] Autoproteolytic activity of P2 enables cis cleavage of P1234 between P3 and P4, forming a P123 polyprotein and a nsP4 protein. The nsP4 protein is an RNA-dependent RNA polymerase and promotes further negative-strand RNA synthesis. This leads to the accumulation of P123 over time and once the concentration is high enough, all the other proteins are cleaved by the trans proteolytic activity of P2. Finally, the N-terminal of nsP4 is able to act as a scaffold and forms a complex with nsP1, nsP2, and nsP3 that then causes plus strand synthesis.

The formation of a subgenomic fragment, encoding the structural proteins and a negative-sense fragment, a template for further synthesis of positive-sense RNA, is the characteristic second phase of translation. Assembly takes place at the cell surface, where the virus buds from the cell, acquiring the envelope. The replication cycle is very fast, taking around 4 hours.[4][5]

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.[4] Rubella virus was formerly included in the family Togaviridae in its own genus Rubivirus, but is now classified in its own family Matonaviridae[7]

• 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—Norman Gregg notices large number of children with 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 miles (64 km) north of Cairo, Egypt.
• 1959—Ross River virus is isolated from Aedes vigilax mosquitoes (now known as Ochlerotatus vigilax[8]) 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.[9]
• 1971—Last epidemic of Venezuelan equine encephalitis is seen in horses in southern Texas.[10]

• 1986—Barmah Forest virus is identified as causing human disease in Australia.[11]

• 2001—Scientists solved the crystal structure of the glycoprotein shell of 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[12]

• 2006—Major epidemic of the chikungunya virus in India with over 1.5 million cases reported[13]

• ICTV Report Togaviridae</>
• Togaviridae Genomes database search results from the Viral Bioinformatics Resource Center
• Viralzone: Togaviridae
• Virus Pathogen Database and Analysis Resource (ViPR): Togaviridae
• "Togaviridae". NCBI Taxonomy Browser. 11018.
• Jose, J.; Snyder, J. E.; Kuhn, R. J. (2009). "A structural and functional perspective of alphavirus replication and assembly". Future Microbiology. 4 (7): 837–856. doi:10.2217/fmb.09.59. PMC 2762864. PMID 19722838.