Mammalian orthoreovirus infection is enhanced in cells pre-treated with sodium arsenite

Following reovirus infection, cells activate stress responses that repress canonical cellular translation as a mechanism to limit production of progeny virions. This includes the formation of stress granules (SG) that sequester translationally-stalled cellular transcripts, translation initiation factors, ribosomal proteins, and RNA binding proteins until conditions improve and translation can resume. Work by others suggests that these cellular stress responses, which are part of the integrated stress response, may benefit rather than repress reovirus replication. In agreement with this, we report that stressing cells prior to infection with sodium arsenite (SA), a robust inducer of SG and activator of eIF2α kinases, enhanced viral protein expression, percent infectivity and viral titer in SA-treated cells compared to untreated cells. SA-mediated enhancement of reovirus replication was not strain-specific, but was cell-type specific. While pre-treatment of cells with SA offered the greatest enhancement, treatment of infected cultures as late as 4 h post infection resulted in an increase in the percent of cells infected. SA activates the HRI kinase, which phosphorylates eIF2α and subsequently induces SG formation. Other stresses, such as heat shock (HS) and osmotic shock also activate HRI. Heat shock of cells prior to reovirus infection readily induced SG in greater than 85% of cells. Although HS pre-treatment had no effect on the percentage of infected cells or viral yield, it did enhance viral protein expression. These data suggest that SA pre-treatment perturbs the cell in a way that is beneficial for reovirus and that neither HRI activation nor SG induction is sufficient for reovirus infection enhancement.