Phosphorylation at the Homotypic Interface Regulates Nucleoprotein Oligomerization and Assembly of the Influenza Virus Replication Machinery

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Replication and transcription by negative-sense RNA viruses occurs in large macromolecular complexes. These complexes contain the viral polymerase, genomic RNA, and multiple copies of nucleoprotein that bind RNA and oligomerize to coat the genome. For influenza virus, nucleoprotein (NP) non-specifically binds nucleic acids and spontaneously oligomerizes. It is essential that a portion of NP be maintained as a monomer so that it can selectively oligomerize into replication complexes. Despite the fact that this process must be tightly regulated during the viral life cycle, how this regulation is achieved is largely unknown. Here we show that phosphorylation of NP negatively regulates assembly of the influenza virus replication machinery. We identified two phosphorylation sites on opposite sides of the NP:NP interface and showed that phosphorylation at either site blocks homotypic interactions, distorting the monomer:oligomer balance of NP in cells and severely impairing virus replication. Our findings show that the phospho-regulated conversion of NP between mono- and oligomeric states is important for RNP formation, gene expression and viral replication. Moreover, we showed that these critical phosphorylation sites play the same role in influenza B virus and are likely present in influenza C and D viruses, suggesting our results are broadly applicable across viral strains and genera and reveal a global regulatory strategy for Orthomyxoviridae.

Vyšlo v časopise: Phosphorylation at the Homotypic Interface Regulates Nucleoprotein Oligomerization and Assembly of the Influenza Virus Replication Machinery. PLoS Pathog 11(4): e32767. doi:10.1371/journal.ppat.1004826
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004826

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