Elsevier

Virology

Volume 485, November 2015, Pages 104-115
Virology

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

https://doi.org/10.1016/j.virol.2015.06.032Get rights and content
Under an Elsevier user license
open archive

Highlights

  • Polymerase inhibitory effect of BNP is correlated with its binding to ANP.

  • Tail loops and receptors of both NPs are critical for intertypic NP binding.

  • Phosphorylation of BNP does not abolish intertypic NP binding.

  • NP blocks ANP׳s interaction with the PB2 polymerase subunit.

  • BNP׳s antiviral effect is specific to influenza A viruses.

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׳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׳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.

Keywords

Intertypic interference
Influenza virus
Nucleoprotein

Cited by (0)

1

These authors contributed equally to this work.