Structure and receptor-binding properties of an airborne transmissible avian infl uenza A virus hemagglutinin H5(VN1203mut)  

作　　者：Xishan Lu Yi Shi Wei Zhang Yanfang Zhang Jianxun Qi George F Gao 

机构地区：[1]College of Veterinary Medicine,China Agricultural University,Beijing 100193,China [2]Research Network of Immunity and Health(RNIH),Beijing Institutes of Life Science,Chinese Academy of Sciences,Beijing 100101,China [3]CAS Key Laboratory of Pathogenic Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,Beijing 100101,China [4]University of Chinese Academy of Sciences,Chinese Academy of Sciences,Beijing 100049,China [5]Laboratory of Protein Engineering and Vaccines,Tianjin Institute of Industrial Biotechnology,Chinese Academy of Sciences,Tianjin 300308,China [6]National Institute for Viral Disease Control and Prevention,Chinese Center for Disease Control and Prevention(China CDC),Beijing 102206,China

出　　处：《Protein & Cell》2013年第7期502-511,共10页蛋白质与细胞（英文版）

基　　金：the National Basic Research Program(973 Program)(No.2011CB504703);the National Natural Sci-ence Foundation of China(Grant No.81290342);.G.F.G.is a leading principal investigator of the NSFC Innovative Research Group(Grant No.81021003)。

摘　　要：Avian infl uenza A virus continues to pose a global threat with occasional H5N1 human infections,which is em-phasized by a recent severe human infection caused by avian-origin H7N9 in China.Luckily these viruses do not transmit effi ciently in human populations.With a few ami-no acid substitutions of the hemagglutinin H5 protein in the laboratory,two H5 mutants have been shown to obtain an air-borne transmission in a mammalian ferret model.Here in this study one of the mutant H5 proteins devel-oped by Kawaoka’s group(VN1203mut)was expressed in a baculovirus system and its receptor-binding properties were assessed.We herein show that the VN1203mut had a dramatically reduced binding affi nity for the avianα2,3-linkage receptor compared to wild type but showed no detectable increase in affi nity for the humanα2,6-linkage receptor,using Surface Plasmon Resonance techonology.Further,the crystal structures of the VN1203mut and its complexes with either human or avian receptors demon-strate that the VN1203mut binds the human receptor in the same binding manner(cis conformation)as seen for the HAs of previously reported 1957 and 1968 pandemic influenza viruses.Our receptor binding and crystallo-graphic data shown here further confi rm that the ability to bind the avian receptor has to decrease for a higher hu-man receptor binding affi nity.As the Q226L substitution is shown important for obtaining human receptor binding,we suspect that the newly emerged H7N9 binds human receptor as H7 has a Q226L substitution.

关 键 词：AIRBORNE transmission H5 avian infl uenza STRUCTURE receptor binding 

分 类 号：R73[医药卫生—肿瘤]