title: Tyrosines in the influenza A virus M2 protein cytoplasmic tail are critical for production of infectious virus particles.
abstract: The cytoplasmic tail of the influenza A virus M2 protein is required for the production of infectious virions. In this study, critical residues in the M2 cytoplasmic tail were identified by single-alanine scanning mutagenesis. The tyrosine residue at position 76, which is conserved in >99% of influenza virus strains sequenced to date, was identified as being critical for the formation of infectious virus particles using both reverse genetics and a protein trans-complementation assay. Recombinant viruses encoding M2 with the Y76A mutation demonstrated replication defects in MDCK cells as well as in primary differentiated airway epithelial cell cultures, defects in the formation of filamentous virus particles, and reduced packaging of nucleoprotein into virus particles. These defects could all be overcome by a mutation of serine to tyrosine at position 71 of the M2 cytoplasmic tail, which emerged after blind passage of viruses containing the Y76A mutation. These data confirm and extend our understanding of the significance of the M2 protein for infectious virus particle assembly.
authors.affiliation: W Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University, Bloomberg School of Public Health, 615 North Wolfe Street, Suite 5132, Baltimore, Maryland 21205, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Grantham
authors.forename: Shaun M
authors.initials: SM
authors.lastname: Stewart
authors.forename: Erin N
authors.initials: EN
authors.lastname: Lalime
authors.forename: Andrew
authors.initials: A
authors.lastname: Pekosz
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D006801:Humans; D009980:Influenza A virus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D007251:Influenza, Human / Q000821:virology; D009154:Mutation; D014443:Tyrosine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D019065:Virus Assembly; D014779:Virus Replication; D000086082:Viroporin Proteins
chemical_list: D014443:Tyrosine; D014763:Viral Matrix Proteins; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins