Alphaviruses

The alphaviruses are principally mosquito-borne, positive-strand RNA viruses in the family Togaviridae that exhibit a broad range of pathogenicity in humans and animals. The replication complexes of alphaviruses are associated with cytoplasmic membranes, and the main determinant of membrane attachment seems to be nsP1, which is hydrophobically modified by palmitoylation of cysteine residues. In humans, an age-dependent susceptibility of infants and the elderly to central nervous system (CNS) infection has been observed epidemiologically, although its pathogenesis has not been elucidated. Immature mouse neurons infected with Sindbis Virus (SINV) or Semliki Forest Virus (SFV) die of caspase-dependent apoptosis, while mature neurons survive by producing factors inhibiting virus-induced apoptosis. Apoptosis is induced at the time of alphavirus fusion with the cell membrane, and virus replication is not required. Mayaro virus (MAYV) is the principal New World representative of alphaviruses within the SFV complex. The epidemiological pattern is explained by the forest cycle of viral transmission, probably between Hemagogus mosquitoes and wild vertebrates, including monkeys and marmosets, analogous to the sylvatic cycle of yellow fever. The majority of infections with the arthritogenic alphaviruses are benign but temporarily debilitating. Barmah Forest virus (BFV), named after the site in northern Victoria where it was first isolated from Culex annulirostris mosquitoes, is antigenically distinct from other alphaviruses, including River virus (RRV) and SINV, that are also found in Australia. Alphaviruses principally are maintained in zoonotic transmission cycles in natural habitats.