Abstract
Protein modifications dynamically occur and regulate biological processes in all organisms. Towards understanding the significance of protein modifications in influenza virus infection, we performed a global mass spectrometry screen followed by bioinformatics analyses of acetylation, methylation and allysine modification in human lung epithelial cells in response to influenza A virus infection. We discovered 8 out of 10 major viral proteins and 245 out of 2280 host proteins detected to be differentially modified by three modifications in infected cells. Some of the identified proteins were modified on multiple amino acids residues and by more than one modification; the latter occurred either on different or same residues. Most of the modified residues in viral proteins were conserved across >40 subtypes of influenza A virus, and influenza B or C viruses and located on the protein surface. Importantly, many of those residues have already been determined to be critical for the influenza A virus. Similarly, many modified residues in host proteins were conserved across influenza A virus hosts like humans, birds, and pigs. Finally, host proteins undergoing the three modifications clustered in common functional networks of metabolic, cytoskeletal, and RNA processes, all of which are known to be exploited by the influenza A virus.