Influenza B virus non-structural protein 1 counteracts ISG15 antiviral activity by sequestering ISGylated viral proteins

Citations Over TimeTop 10% of 2016 papers

Abstract

The ubiquitin-like protein ISG15 and its conjugation to proteins (ISGylation) are strongly induced by type I interferon. Influenza B virus encodes non-structural protein 1 (NS1B) that binds human ISG15 and provides an appropriate model for determining how ISGylation affects virus replication in human cells. Here using a recombinant virus encoding a NS1B protein defective in ISG15 binding, we show that NS1B counteracts ISGylation-mediated antiviral activity by binding and sequestering ISGylated viral proteins, primarily ISGylated viral nucleoprotein (NP), in infected cells. ISGylated NP that is not sequestered by mutant NS1B acts as a dominant-negative inhibitor of oligomerization of the more abundant unconjugated NP. Consequently formation of viral ribonucleoproteins that catalyse viral RNA synthesis is inhibited, causing decreased viral protein synthesis and virus replication. We verify that ISGylated NP is largely responsible for inhibition of viral RNA synthesis by generating recombinant viruses that lack known ISGylation sites in NP.

Related Papers

• → Identification of the domains of the influenza A virus M1 matrix protein required for NP binding, oligomerization and incorporation into virions(2007)156 cited
• → Single-Particle Tracking Demonstrates that Actin Coordinates the Movement of the Ebola Virus Matrix Protein(2012)50 cited
• → Molecular Mechanism of Arenavirus Assembly and Budding(2012)46 cited
• → Structure and Functions of the Ebola Virus Matrix Protein VP40(2018)8 cited
• → Structural studies on the Ebola virus matrix protein VP40 indicate that matrix proteins of enveloped RNA viruses are analogues but not homologues(2004)27 cited