A structural and functional perspective of alphavirus replication and assembly

Abstract

Alphaviruses are small, spherical, enveloped, positive-sense ssRNA viruses responsible for a considerable number of human and animal diseases. Alphavirus members include Chikungunya virus, Sindbis virus, Semliki Forest virus, the western, eastern and Venezuelan equine encephalitis viruses, and the Ross River virus. Alphaviruses can cause arthritic diseases and encephalitis in humans and animals and continue to be a worldwide threat. The viruses are transmitted by blood-sucking arthropods, and replicate in both arthropod and vertebrate hosts. Alphaviruses form spherical particles (65–70 nm in diameter) with icosahedral symmetry and a triangulation number of four. The icosahedral structures of alphaviruses have been defined to very high resolutions by cryo-electron microscopy and crystallographic studies. In this review, we summarize the major events in alphavirus infection: entry, replication, assembly and budding. We focus on data acquired from structural and functional studies of the alphaviruses. These structural and functional data provide a broader perspective of the virus lifecycle and structure, and allow additional insight into these important viruses.

Viperin restricts chikungunya virus replication and pathology

“…However, contrary to other infections, such as with human cytomegalovirus (27), viperin was not redistributed after CHIKV infection, indicative of a different mode of antiviral action. Furthermore, replication complexes of alphaviruses have been reported to localize in the proximity of the ER in order to drive synthesis and replication of viral genomes, leading to consequential translation of the viral structural proteins at the ER required for packaging and formation of new virus progeny (56,57). In addition, we demonstrated that CHIKV nsP2, a RNA helicase/protease mediating replication, colocalized around the periphery of the ER during CHIKV infection.…”

Chikungunya virus non-structural protein 2-mediated host shut-off disables the unfolded protein response

“…After autocatalytic cleavage of the capsid protein, the remaining polyprotein translocates to the ER. In the ER, the polyprotein is cleaved by host signalases into precursors E2 and E1, which are N-linked glycosylated before being transported to the Golgi network (Jose et al, 2009;Metz et al, 2011). We investigated whether CHIKV envelope glycoproteins induced the UPR and whether CHIKV replication affected UPR target gene expression and the expression of ATF4.…”

Current Strategic Thinking for the Development of a Trivalent Alphavirus Vaccine for Human Use

“…Alphaviruses use a single-stranded positivesense RNA genome that encodes four non-structural and five structural proteins. 2 These viruses are zoonotic pathogens that are maintained by mosquitoes and birds (WEEV and EEEV) or mammals (VEEV) in an enzootic lifecycle. 3 Depending on climate conditions, mosquito species, and/or virus strain, they can also be transmitted to horses and humans by spillover of enzootic transmission or in an equine-amplified epizootic cycle, causing severe encephalitis in some cases.…”