gnarled-trunk evolutionary model of influenza a virus hemagglutiningnarled-trunk甲型流感病毒血凝素的进化模型.pdfVIP

Gnarled-Trunk Evolutionary Model of Influenza A Virus Hemagglutinin 1,2 1 3 1 1 1,4,5,6 Kimihito Ito , Manabu Igarashi , Yutaka Miyazaki , Teiji Murakami , Syaka Iida , Hiroshi Kida , Ayato Takada1,7* 1 Hokkaido University Research Center for Zoonosis Control, Sapporo, Japan, 2 PRESTO, Japan Science and Technology Agency, Saitama, Japan, 3 Faculty of Liberal Arts and Sciences, Osaka University of Economics and Law, Yao, Japan, 4 Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan, 5 OIE Reference Laboratory for Highly Pathogenic Avian Influenza, Sapporo, Japan, 6 SORST, Japan Science and Technology Agency, Saitama, Japan, 7 School of Veterinary Medicine, The University of Zambia, Lusaka, Zambia Abstract Human influenza A viruses undergo antigenic changes with gradual accumulation of amino acid substitutions on the hemagglutinin (HA) molecule. A strong antigenic mismatch between vaccine and epidemic strains often requires the replacement of influenza vaccines worldwide. To establish a practical model enabling us to predict the future direction of the influenza virus evolution, relative distances of amino acid sequences among past epidemic strains were analyzed by multidimensional scaling (MDS). We found that human influenza viruses have evolved along a gnarled evolutionary pathway with an approximately constant curvature in the MDS-constructed 3D space. The gnarled pathway indicated that evolution on the trunk favored multiple substitutions at the same amino acid positions on HA. The constant curvature was reasonably explained by assuming that the rate of a