Genome-wide mutagenesis of influenza virus reveals unique plasticity of the hemagglutinin and NS1 proteins

Nicholas S. Heaton, David Sachs, Chi Jene Chen, Rong Hai, Peter Palese

Research output: Contribution to journalArticlepeer-review

149 Scopus citations

Abstract

The molecular basis for the diversity across influenza strains is poorly understood. To gain insight into this question, we mutagenized the viral genome and sequenced recoverable viruses. Only two small regions in the genome were enriched for insertions, the hemagglutinin head and the immune-modulatory nonstructural protein 1. These proteins play a major role in host adaptation, and thus need to be able to evolve rapidly. We propose a model in which certain influenza A virus proteins (or protein domains) exist as highly plastic scaffolds, which will readily accept mutations yet retain their functionality. This model implies that the ability to rapidly acquire mutations is an inherent aspect of influenza HA and nonstructural protein 1 proteins; further, this may explain why rapid antigenic drift and a broad host range is observed with influenza A virus and not with some other RNA viruses.

Original languageEnglish
Pages (from-to)20248-20253
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number50
DOIs
StatePublished - 10 Dec 2013

Keywords

  • Insertional mutagenesis
  • Protein flexibility
  • Viral evolution

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