West Nile virus infection does not induce PKR activation in rodent cells

dsRNA-activated protein kinase (PKR) is activated by viral dsRNAs and phosphorylates eIF2a reducing translation of host and viral mRNA. Although infection with a chimeric West Nile virus (WNV) efficiently induced PKR and eIF2a phosphorylation, infections with natural lineage 1 or 2 strains did not. Investigation of the mechanism of suppression showed that among the cellular PKR inhibitor proteins tested, only Nck, known to interact with inactive PKR, colocalized and co-immunoprecipitated with PKR in WNV-infected cells and PKR phosphorylation did not increase in infected Nck1,2−/− cells. Several WNV stem-loop RNAs efficiently activated PKR in vitro but not in infected cells. WNV infection did not interfere with intracellular PKR activation by poly(I:C) and similar virus yields were produced by control and PKR−/− cells. The results indicate that PKR phosphorylation is not actively suppressed in WNV-infected cells but that PKR is not activated by the viral dsRNA in infected cells.

► PKR is upregulated in WNV-infected cells, but PKR phosphorylation is not induced.
► The association of PKR with Nck in WNV-infected cells indicates that PKR is inactive.
► WNV stem-loop RNAs efficiently activate PKR in vitro but not in infected cells.
► WNV infection does not interfere with poly(I:C)-mediated PKR activation.
► WNV yields were similar from wild type and PKR−/− MEFs.