title: Genome-wide mutagenesis of influenza virus reveals unique plasticity of the hemagglutinin and NS1 proteins.
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.
authors.affiliation: Departments of Microbiology, Genetics, and Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Heaton
authors.forename: David
authors.initials: D
authors.lastname: Sachs
authors.forename: Chi-Jene
authors.initials: CJ
authors.lastname: Chen
authors.forename: Rong
authors.initials: R
authors.lastname: Hai
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
mesh_terms: D000220:Adaptation, Biological / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004285:Dogs; D019143:Evolution, Molecular; D005814:Genes, Viral / Q000235:genetics; D016679:Genome, Viral / Q000235:genetics*; D057809:HEK293 Cells; D006388:Hemagglutinins / Q000235:genetics; D006801:Humans; D009980:Influenza A virus / Q000235:genetics*; D061985:Madin Darby Canine Kidney Cells; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D017361:Viral Nonstructural Proteins / Q000235:genetics*
chemical_list: D017931:DNA Primers; D006388:Hemagglutinins; C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins
keywords: insertional mutagenesis; protein flexibility; viral evolution