Alphavirus structure, replication and transmission cycles

Structure and replication

Alphavirus is a genus of arthropod-borne viruses (arboviruses) in the family Togaviridae (Calisher et al., 1980; Calisher & Karabatsos, 1988). These viruses have unsegmented, single-stranded RNA genomes of 11–12 kb which are of positive or messenger sense. Alphavirus genomic RNA encodes four non-structural proteins, designated nsP1–4, as well as three structural proteins: the capsid, and two envelope glycoproteins, El and E2 (Fig. 33.1). A sub-genomic 26S RNA species, which encodes only the structural proteins, is also produced in infected cells.

Alphaviruses replicate in the cytoplasm of infected cells. Entry into vertebrate cells occurs via receptor-mediated endocytosis (Kielian & Helenius, 1986). The high-affinity laminin receptor serves as a mammalian and mosquito cell (in vitro) receptor for the alphavirus, Sindbis (SIN) (Wang et al., 1992), whereas other protein receptors for SIN have been identified in mouse neural (Ubol & Griffin, 1991) and chicken cells (Wang et al., 1991). Wang et al. (1992) believe that the wide host range of Sindbis virus is the result of its utilization of a highly conserved receptor, found in a variety of vertebrates and in mosquito cells (laminin receptor), as well as its use of multiple receptors. The mechanism of alphavirus entry into mosquito cells has not been identified, although the very specific infectivity patterns of some alphaviruses for their mosquito vectors suggest use of a less conserved protein receptor during initial infection of the midgut.

Genomic alphavirus RNA is translated by cellular components to produce the non-structural proteins, and also serves as a template for minus-strand RNA synthesis involving the non-structural proteins.