Palmitoylation of the influenza A virus M2 protein is not required for virus replication in vitro but contributes to virus virulence.
The influenza A virus M2 protein has important roles during virus entry and in the assembly of infectious virus particles. The cytoplasmic tail of the protein can be palmitoylated at a cysteine residue, but this residue is not conserved in a number of human influenza A virus isolates. Recombinant viruses encoding M2 proteins with a serine substituted for the cysteine at position 50 were generated in the A/WSN/33 (H1N1) and A/Udorn/72 (H3N2) genetic backgrounds. The recombinant viruses were not attenuated for replication in MDCK cells, Calu-3 cells, or in primary differentiated murine trachea epithelial cell cultures, indicating there was no significant contribution of M2 palmitoylation to virus replication in vitro. The A/WSN/33 M2C50S virus displayed a slightly reduced virulence after infection of mice, suggesting that there may be novel functions for M2 palmitoylation during in vivo infection.
Grantham
Michael L
ML
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University, Bloomberg School of Public Health, 615 North Wolfe St., Baltimore, MD 21205, USA.
Wu
Wai-Hong
WH
Lalime
Erin N
EN
Lorenzo
Maria E
ME
Klein
Sabra L
SL
Pekosz
Andrew
A
D019943:Amino Acid Substitution; D000818:Animals; D001835:Body Weight; D002460:Cell Line; D002478:Cells, Cultured; D004285:Dogs; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000472:pathogenicity / Q000502:physiology*; D053122:Influenza A Virus, H3N2 Subtype / Q000472:pathogenicity / Q000502:physiology*; D054878:Lipoylation; D008168:Lung / Q000821:virology; D051379:Mice; D016297:Mutagenesis, Site-Directed; D009976:Orthomyxoviridae Infections / Q000473:pathology / Q000821:virology; D016019:Survival Analysis; D014763:Viral Matrix Proteins / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism*; D014779:Virus Replication; D000086082:Viroporin Proteins
D014763:Viral Matrix Proteins; D037521:Virulence Factors; C488937:M2 protein, Influenza A virus; D000086082:Viroporin Proteins