Induction of type I IFN response by alphavirus replicases in the absence of viral RNA templates

Abstract

Alphaviruses are arthropod transmitted viruses with global distribution and wide host range. Upon infection, some alphaviruses may cause acute muscle pain, arthritis, rash, and encephalitis. In the past decades alphavirus-caused epidemics are not uncommon, but despite that there are currently no licensed vaccines or antiviral drugs for any of the alphavirus species. During viral replication and transcription, alphavirus replicase generates 5’-triphosphate RNA and double-stranded RNA (dsRNA), which trigger type I interferon production. Remarkably, it has been shown that SFV and SINV replicases induce IFN- response in absence of viral RNA templates by generating 5’-ppp dsRNA from host cell RNA. In the current work we investigated whether some other alphavirus replicases possess such property and how it differs in human and insect cells. We observed that other alphavirus replicases can generate IFN-inducing RNA without presence of viral RNA templates. We also concluded that correlation between replicase’s ability to transcribe and replicate viral RNA template and its ability to synthesize IFN-inducing RNA from host’s cellular RNA is not universal attribute of all alphaviruses.