Tyrosines in the influenza A virus M2 protein cytoplasmic tail are critical for production of infectious virus particles

Michael L. Grantham, Shaun M. Stewart, Erin N. Lalime, Andrew Pekosz

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)8765-8776
Number of pages12
JournalJournal of Virology
Volume84
Issue number17
DOIs
StatePublished - Sep 2010

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virion
Influenza A virus
Virion
Tyrosine
tyrosine
tail
mutation
proteins
Mutation
Viruses
Virus Assembly
Reverse Genetics
viruses
nucleoproteins
Madin Darby Canine Kidney Cells
Nucleoproteins
Product Packaging
Orthomyxoviridae
mutagenesis
Mutagenesis

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Tyrosines in the influenza A virus M2 protein cytoplasmic tail are critical for production of infectious virus particles. / Grantham, Michael L.; Stewart, Shaun M.; Lalime, Erin N.; Pekosz, Andrew.

In: Journal of Virology, Vol. 84, No. 17, 09.2010, p. 8765-8776.

Research output: Contribution to journalArticle

Grantham, Michael L. ; Stewart, Shaun M. ; Lalime, Erin N. ; Pekosz, Andrew. / Tyrosines in the influenza A virus M2 protein cytoplasmic tail are critical for production of infectious virus particles. In: Journal of Virology. 2010 ; Vol. 84, No. 17. pp. 8765-8776.
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