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.
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.Genus Structure Symmetry Capsid Genomic arrangement Genomic segmentation Alphavirus Icosahedral T=4 Enveloped Linear Monopartite Rubivirus Icosahedral T=4 Enveloped Linear Monopartite
Entry into the host cell is achieved by attachment of the viral E glycoprotein to host receptors, which mediates clathrin-mediated endocytosis. 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.
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. Human, mammals, marsupials, birds, and mosquitoes serve as the natural host. Transmission routes are zoonosis, bite, and respiratory.Genus Host details Tissue tropism Entry details Release details Replication site Assembly site Transmission Alphavirus Humans; mammals; marsupials; birds; mosquitoes None Clathrin-mediated endocytosis Secretion Cytoplasm Cytoplasm Zoonosis: arthropod bite Rubivirus Humans None Clathrin-mediated endocytosis Secretion Cytoplasm Cytoplasm Aerosol
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. 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.
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.