Mechanistic study of intertypic nucleoprotein complex formation and its inhibitory effect toward influenza A virus

Issue Date

11-2015

Abstract

Co-infection of influenza A and B viruses (IAV and IBV) results in marked decreases in IAV replication. Multiple mechanisms have been proposed for this phenomenon. Recently, we reported that IBV nucleoprotein (BNP) alone can suppress IAV replication and proposed an inhibition model in which BNP binds IAV nucleoprotein (ANP) and disrupts IAV polymerase complexes. Here, using mutagenesis and co-immunoprecipitation, we determined the protein motifs mediating the intertypic ANP-BNP complex and showed that it specifically interferes with ANP[U+05F3]s interaction with the PB2 subunit of the IAV polymerase but not with the other subunit PB1. We further demonstrated that BNP only suppresses growth of IAVs but not other RNA viruses. However, different IAV strains display varied sensitivity toward the BNP[U+05F3]s inhibitory effect. Together, our data provide mechanistic insights into intertypic nucleoprotein complex formation and highlight the role of BNP as a potential broad-spectrum anti-IAV agent.

Source or Periodical Title

Virology

ISSN

0042-6822

Volume

485

Page

104-115

Document Type

Article

Language

English

Subject

Influenza virus, Intertypic interference, Nucleoprotein

Identifier

doi:10.1016/j.virol.2015.06.032.

Digital Copy

yes

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