Alphavirus Infection: Host Cell Shut-Off and Inhibition of Antiviral Responses.
Alphaviruses cause debilitating disease in humans and animals and are transmitted by blood-feeding arthropods, typically mosquitoes. With a traditional focus on two models, Sindbis virus and Semliki Forest virus, alphavirus research has significantly intensified in the last decade partly due to the re-emergence and dramatic expansion of chikungunya virus in Asia, Europe, and the Americas. As a consequence, alphavirus-host interactions are now understood in much more molecular detail, and important novel mechanisms have been elucidated. It has become clear that alphaviruses not only cause a general host shut-off in infected vertebrate cells, but also specifically suppress different host antiviral pathways using their viral nonstructural proteins, nsP2 and nsP3. Here we review the current state of the art of alphavirus host cell shut-off of viral transcription and translation, and describe recent insights in viral subversion of interferon induction and signaling, the unfolded protein response, and stress granule assembly.
Nuffield Department of Medicine, Peter Medawar Building for Pathogen Research, University of Oxford, Oxford OX1 3SY, England, UK. jelke.fros@ndm.ox.ac.uk.|Laboratory of Virology, Wageningen University, Droevendaalsesteeg 1, 6708 PB, Wageningen 6700 AB, The Netherlands. jelke.fros@ndm.ox.ac.uk.
Jelke J
JJ
Fros
Laboratory of Virology, Wageningen University, Droevendaalsesteeg 1, 6708 PB, Wageningen 6700 AB, The Netherlands. gorben.pijlman@wur.nl.
Gorben P
GP
Pijlman
D000524:Alphavirus / Q000472:pathogenicity*; D018354:Alphavirus Infections / Q000276:immunology* / Q000821:virology*; D000818:Animals; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D037521:Virulence Factors / Q000378:metabolism
D017361:Viral Nonstructural Proteins; D037521:Virulence Factors
Semliki Forest; Sindbis; alphavirus; antiviral response; chikungunya; host shut-off; interferon; stress granules; transcription; translation; unfolded protein response