Analysis of Influenza A/Beijing/353/89 Virus Matrix Gene Sequence and Identification of Replaceable Amino Acids as Natural Mutations in M2 Protein

The influenza virus A/Beijing/353/89 matrix (M), M1 and M2 genes were cloned and sequenced. The sequence identity rates (based on published data) of the first 34 influenza A viruses with M genes most phylogenetically related to A/Beijing/353/89 virus were in significant positive correlation among M, M1 and M2 genes and M1 protein but not M2 protein. The number of viruses with M2 protein sequences identical to influenza A/Beijing/353/89 virus was significantly higher than those with identical M2 gene and M1 protein sequences (P<0.01). These results suggest that natural variation of M2 protein did not occur entirely in random. Based on a statistical standard we have established and using the A/Beijing/353/89 M2 as reference protein, 35 replaceable amino acids were identified by analysis of 193 published influenza A virus M2 protein sequences. In contrast, it is more possible that those critical amino acids for virus survival and/or replication harbored in the 24 amino acids, which were not yet found to have ever been substituted.