Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes fatal infections in humans. As with most disease-causing viruses, the pathogenic potential of NiV is linked to its ability to block antiviral responses, e.g., by antagonizing IFN signaling through blocking STAT proteins. One of the STAT1/2-binding proteins of NiV is the phosphoprotein (P), but its functional role in IFN antagonism in a full viral context is not well defined. As NiV P is required for genome replication and specifically accumulates in cytosolic inclusion bodies (IBs) of infected cells, we hypothesized that this compartmentalization might play a role in P-mediated IFN antagonism. Supporting this notion, we show here that NiV can inhibit IFN-dependent antiviral signaling via a NiV P-dependent sequestration of STAT1 and STAT2 into viral IBs. Consequently, the phosphorylation/activation and nuclear translocation of STAT proteins in response to IFN is limited, as indicated by the lack of nuclear pSTAT in NiV-infected cells. Blocking autocrine IFN signaling by sequestering STAT proteins in IBs is a not yet described mechanism by which NiV could block antiviral gene expression and provides the first evidence that cytosolic NiV IBs may play a functional role in IFN antagonism.
Keywords: IFN; Nipah virus; STAT1; STAT2; autocrine signaling; inclusions; phosphoprotein.