Study on the Receptor Binding Specificity and Structural Basis of H5N1 Avian Influenza Virus Hemagglutinin Protein

H5N1 highly pathogenic avian influenza virus has been an important pathogen hazard of poultry industry in China, and its interspecies transmission to human has posed a serious threat to public health. Hemagglutinin (HA) -mediated receptor binding is a major determinant of influenza virus interspecies transmission. In 2013, we determined the complex structures of a mutant HA from a ferret-transmissible H5N1 virus bound to either avian or human receptor sialic acid analogs, providing a structural basis to understand how Q226L substitution alters the receptor binding preference of H5N1 HA. However, there are still many amino acid substitutions which can alter the receptor binding specificity of H5N1 HA, and the molecular mechanisms of these changing have not been elucidated. . Here, we have expressed the HA of an H5N1 virus isolated from Qinghai Lake (QH05-H5) and solved its crystal structure. Our project is to introduce amino acid substitutions into the QH05-H5 to general mutants which may obtain human receptor binding specificity, and screen positive mutants by examining the receptor binding properties of these mutant H5 proteins as well as H5N1 pseudoviruses. We will also solve the complex structures of positive mutants bound to human receptor analogs to provide the structural basises for the H5 adaptations to acquire human receptor binding properties. Our research will elucidate the molecular mechanisms of interspecies transmission of H5N1 influenza virus, and provide an important theoretical basis for the monitoring and early warning of the pandemic of H5N1 influenza virus in human.