Nov 15, 2019

Antagonism of STAT1 by Nipah virus P gene products modulates disease course but not lethal outcome in the ferret model

Scientific Reports
Benjamin A SatterfieldChad E Mire

Abstract

Nipah virus (NiV) is a pathogenic paramyxovirus and zoononis with very high human fatality rates. Previous protein over-expression studies have shown that various mutations to the common N-terminal STAT1-binding motif of the NiV P, V, and W proteins affected the STAT1-binding ability of these proteins thus interfering with he JAK/STAT pathway and reducing their ability to inhibit type-I IFN signaling, but due to differing techniques it was unclear which amino acids were most important in this interaction or what impact this had on pathogenesis in vivo. We compared all previously described mutations in parallel and found the amino acid mutation Y116E demonstrated the greatest reduction in binding to STAT1 and the greatest reduction in interferon antagonism. A similar reduction in binding and activity was seen for a deletion of twenty amino acids constituting the described STAT1-binding domain. To investigate the contribution of this STAT1-binding motif in NiV-mediated disease, we produced rNiVs with complete deletion of the STAT1-binding motif or the Y116E mutation for ferret challenge studies (rNiVM-STAT1blind). Despite the reduced IFN inhibitory function, ferrets challenged with these rNiVM-STAT1blind mutants had a lethal, alb...Continue Reading

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Mentioned in this Paper

Study
In Vivo
Nipah Virus
Signal Induction
Pathogenesis
JAK-STAT Pathway Deregulation
Stat1 protein, rat
Molecular_function
Gene Deletion
Mutant Proteins

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