adaption of seasonal h1n1 influenza virus in mice适应季节性h1n1流感病毒的老鼠.pdfVIP

Adaption of Seasonal H1N1 Influenza Virus in Mice 1 1 1 1 1 2 1 1 Lili Xu , Linlin Bao , Fengdi Li , Qi Lv , Yila Ma , Jiangfang Zhou , Yanfeng Xu , Wei Deng , Lingjun 1 1 1 2 1 Zhan , Hua Zhu , Chunmei Ma , Yuelong Shu , Chuan Qin * 1 Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences Comparative Medicine Center, Peking Union Medical Collage; Key Laboratory of Human Disease Comparative Medicine, Ministry of Health; Key Laboratory of Animal Model of Human Diseases, State Administration of Traditional Chinese Medicine, Beijing, China, 2 State Key Laboratory for Molecular Virology and Genetic Engineering, Chinese National Influenza Center, National Institute for Viral Disease Control and Prevention, China Centers for Disease Control, Beijing, China Abstract The experimental infection of a mouse lung with influenza A virus has proven to be an invaluable model for studying the mechanisms of viral adaptation and virulence. The mouse adaption of human influenza A virus can result in mutations in the HA and other proteins, which is associated with increased virulence in mouse lungs. In this study, a mouse-adapted seasonal H1N1 virus was obtained through serial lung-to-lung passages and had significantly increased virulence and pathogenicity in mice. Genetic analysis indicated that the increased virulence of the mouse-adapted virus was attributed to incremental acquisition of three mutations in the HA protein (T89I, N125T, and D221G). However, the mouse adaption of influenza A virus did not change the specificity and affinity of receptor binding and the pH-dependent membrane fusion of HA, as well as the in vitro replication in MDCK cells. N