题目：Influenza virus entry, neutralization and replication
主讲人：Yi Shi, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Influenza viruses are segmented negative-sense RNA viruses in the family of Orthomyxoviridae, and there are four recognized influenza genera denoted A, B, C and D. Influenza A and B viruses, which both have eight genomic RNA segments, can cause widespread seasonal respiratory disease in humans and a considerable financial burden worldwide. Influenza C and D viruses both have seven segments, and influenza C virus infects mainly humans, while influenza D virus infects cattle and swine, potentially infecting humans. Here we revisit what we have known about the influenza hemagglutinin and its binding to the receptors, and recently, we have characterized the H7-reactive B cell repertoire in four donors infected in 2013 and 2014. We found that the H7-specific antibodies play a key role in the naturally-infected patients, and these neutralizing and protective antibodies recognize overlapping residues surrounding the receptor-binding site of hemagglutinin. Only few of the neutralizing antibodies retained activity for the latest viruses isolated in 2016-2017 that have undergone antigenic change, which emphasizes the need for updated H7N9 vaccines. In addition, we determined the apo and promoter-bound influenza D virus polymerase structures by cryo-EM method, and found that the polymerase has an evolutionarily conserved stable core structure with inherently flexible peripheral domains. Importantly, we found that the RNA promoters can bind in different conformations which are involved in regulation of synthesis of different RNA species. This finding advances our understanding of RNA synthesis by influenza virus polymerase, and opens new opportunities for antiviral drug design.