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
• Genus Rubivirus; type species: Rubella virus

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The Togaviridae family belong to group IV of the Baltimore classification of viruses. The genome is linear, 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 (65-70nm diameter), the capsid within is icosahedral, constructed of 240 monomers, having a triangulation number of 4. The receptors for binding are unknown, however the tropism is varied and it is known that the glycoprotein spikes act as attachment proteins. After virus attachment and entry into the cell, gene expression and replication takes place within the cytoplasm.

Genome replication

The non-structural 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 non-structural proteins responsible for gene expression and replication. The formation of a sub-genomic fragment, encoding the structural proteins and a negative sense fragment, a template for further synthesis of positive sense RNA are 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.

History

Initially the Togavirus 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.

Early 1800s-Rubella is identified as a distinct disease

1930-Western Equine Encephalitis virus is first isolated in the United States (1st 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-Normann 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 north of Cairo, Egypt.

1959-Ross River virus is isolated from Aedes vigilax mosquitoes which were trapped at the Ross River in Australia.

1962-Rubella virus is isolated in culture.

1963-Ross River virus, which causes epidemic polyarthritis (mostly seen in Australia), is isolated by Doherty and colleagues.

1964-The last major epidemic of Rubella in the United States is seen. Approximately 20,000 infants are left with permanent damage following in-utero rubella exposure.

1969-Rubella vaccine is licensed

1971- Last epidemic of Venezuelan equine encephalitis is seen in horses in southern Texas.

1972- The rubella vaccine is combined with the measles and mumps vaccines to form the Measles/Mumps/Rubella (MMR) vaccine.

1986- Barmah Forest virus is identified as causing human disease in Australia.

1991-92- Most recent worldwide epidemic of rubella. Probably due to vaccine failures and missed vaccinations.

References

• University of Leicester, Microbiology
• Stanford University
• Murray, et al, Medical Microbiology, 5th Edition, Philadelphia, Elsevier Mosby 2005 ISBN 0-323-03325-3