Togaviridae

Togaviridae is a family of viruses. Humans, mammals, birds, and mosquitoes serve as natural hosts. There are currently 32 species in this family, divided among 2 genera. Diseases associated with this family include: Alphaviruses: arthritis, encephalitis; Rubiviruses: rubella.^[1][2]

Taxonomy

Group: ssRNA(+)

^[2]

Structure

The Togaviridae family belong to group IV of the Baltimore classification of viruses. The genome is linear, non-segmented, 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]

Life cycle

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

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 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 it’s likely that a few transoceanic crossings have occurred.^[3][4] Human, mammals, marsupials, birds, and mosquitoes serve as the natural host. Transmission routes are zoonosis, bite, and respiratory.^[1]

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. P1234 are the two P123 polyproteins formed. The formation of P1234 occurs due to a stop codon read through, which has a 10% to 20% chance of occurrence.^[5] Auto proteolytic activity of P4 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 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.^[3][4]

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 thanks to the development of sequencing.^[3]

• Early 19th century—Rubella is identified as a distinct disease
• 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 north of Cairo, Egypt.
• 1959—Ross River virus is isolated from Aedes vigilax mosquitoes (now known as Ochlerotatus vigilax^[6]) 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.^[7]

• 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.^[8]
• 1969—Rubella vaccine is licensed
• 1971—Last epidemic of Venezuelan equine encephalitis is seen in horses in southern Texas.^[9]

• 1972—The rubella vaccine is combined with the measles and mumps vaccines to form the Measles, Mumps and Rubella (MMR) vaccine.
• 1986—Barmah Forest virus is identified as causing human disease in Australia.^[10]

• 1991–92—Most recent worldwide epidemic of rubella, probably due to vaccine failures and missed vaccinations.
• 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.^[11]

• 2006—Major epidemic of the chikungunya virus in India with over 1.5 million cases reported.^[12]

References

External links

• Togaviridae Genomes database search results from the Viral Bioinformatics Resource Center
• Viralzone: Togaviridae
• ICTV
• Virus Pathogen Database and Analysis Resource (ViPR): Togaviridae
• "Togaviridae". NCBI Taxonomy Browser. 11018.
• "A structural and functional perspective of alphavirus replication and assembly".