Nipah Virus Impairs Autocrine IFN Signaling by Sequestering STAT1 and STAT2 into Inclusion Bodies.

Abstract

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.