A Novel Role Of Pact In Restriction Of Influenza A Virus Replication

Abstract

Influenza A virus infection causes severe respiratory distress or even deaths every year. Identification of cellular host restriction factors against influenza A virus provides not only a further understanding of host-pathogen interaction but also fundamental knowledge for the control of viral infection. In human, double-stranded RNA (dsRNA) binding protein PACT has been shown to exhibit antiviral activity, possibly through the optimal induction of interferon. In this study, we revealed a novel antiviral role of PACT, which inhibited the influenza A virus replication through a direct interaction with viral dsRNAs. PACT bound to viral dsRNAs both in-vitro and in influenza A virus-infected cells, as demonstrated by RNA-immunoprecipitation and in-vitro pull down assay followed by deep sequencing. Additionally, we assessed the level of viral replication and the activation of interferon signaling in wild-type and PACT-knockout mouse embryonic fibroblasts either infected with wild-type or NS1-deleted influenza A virus. Our data clearly indicated that in the absence of PACT protein expression, viral replication was strongly enhanced in an interferon-independent manner. Taken together, PACT functions as a restriction factor directly interacting with viral dsRNAs/replicating intermediates and hence inhibiting influenza A virus replication. This study was supported by RGC (ECS 27121515, GRF 17153216 and C7011-15R).