title: Entry properties and entry inhibitors of a human H7N9 influenza virus.
abstract: The recently identified human infections with a novel avian influenza H7N9 virus in China raise important questions regarding possible risk to humans. However, the entry properties and tropism of this H7N9 virus were poorly understood. Moreover, neuraminidase inhibitor resistant H7N9 isolates were recently observed in two patients and correlated with poor clinical outcomes. In this study, we aimed to elucidate the entry properties of H7N9 virus, design and evaluate inhibitors for H7N9 virus entry. We optimized and developed an H7N9-pseudotyped particle system (H7N9pp) that could be neutralized by anti-H7 antibodies and closely mimicked the entry process of the H7N9 virus. Avian, human and mouse-derived cultured cells showed high, moderate and low permissiveness to H7N9pp, respectively. Based on influenza virus membrane fusion mechanisms, a potent anti-H7N9 peptide (P155-185-chol) corresponding to the C-terminal ectodomain of the H7N9 hemagglutinin protein was successfully identified. P155-185-chol demonstrated H7N9pp-specific inhibition of infection with IC50 of 0.19 µM. Importantly, P155-185-chol showed significant suppression of A/Anhui/1/2013 H7N9 live virus propagation in MDCK cells and additive effects with NA inhibitors Oseltamivir and Zanamivir. These findings expand our knowledge of the entry properties of the novel H7N9 viruses, and they highlight the potential for developing a new class of inhibitors targeting viral entry for use in the next pandemic.
authors.affiliation: Ministry of Health Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Youhui
authors.initials: Y
authors.lastname: Si
authors.affiliation: Ministry of Health Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Li
authors.affiliation: Ministry of Health Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Ministry of Health Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Liu
authors.affiliation: Ministry of Health Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Ren
authors.affiliation: Ministry of Health Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.affiliation: Ministry of Health Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Cheng
authors.affiliation: Ministry of Health Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Ministry of Health Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Ministry of Health Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Jin
authors.affiliation: Ministry of Health Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
mesh_terms: D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D003412:Cricetulus; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006367:HeLa Cells; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000302:isolation & purification*; D007251:Influenza, Human / Q000821:virology*; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D041681:NIH 3T3 Cells; D009500:Neutralization Tests; D014709:Vero Cells; D053586:Virus Internalization / Q000187:drug effects*