A Coding Theoretical Approach to Predict Sequence Changes in H5N1 Influenza A Virus Hemagglutinin

摘要

The changes in the receptor binding domain of influenza A virus hemagglutinin lead to the appearance of new viral strains that evade the immune system. To prepare the future emergence of potentially dangerous outbreaks caused by divergent influenza strains including human-adapted H5N1 strains, it is imperative that we understand the rule stored in the sequence of the receptor binding domain. Information of life is stored as a sequence of nucleotides, and the sequence composed of four nucleotides seems to be a code. It is important to determine the code structure of the sequences. Once we know the code structure, we can make use of mathematical results concerning coding theory for research in life science. In this study, we applied various codes in coding theory to sequence analysis of the 220 loop in the receptor binding domain of H1, H3, H5 and H7 subtype viruses isolated from humans. Sequence diversity in the 220 loop has been observed even within the same hemagglutinin subtype. However, we found that the code structure of the 220 loop from the same subtype remains unchanged. Our results indicate that the sequences at the 220 loop have the structure of subtype-specific codes. In addition, in view of these finding, we predicted possible amino acid changes in the 220 loop of H5N1 strains that will emerge in the future. Our method will facilitate understanding of the evolutionary patterns of influenza A viruses, and further help the development of new antiviral drugs and vaccines.