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

CORC > 天津工业生物技术研究所 > 蛋白质工程与疫苗实验室高福 > 期刊论文

	Structure and receptor-binding properties of an airborne transmissible avian influenza A virus hemagglutinin H5 (VN1203mut)
	Lu, Xishan 1,3; Shi, Yi 2; Zhang, Wei 3,4; Zhang, Yanfang 5; Qi, Jianxun 3; Gao, George F.1,2,3,4,5,6
刊名	PROTEIN & CELL
	2013-07-01
卷号	4 期号:7 页码:502-511
关键词	airborne transmission H5 avian influenza structure receptor binding
英文摘要	Avian influenza A virus continues to pose a global threat with occasional H5N1 human infections, which is emphasized by a recent severe human infection caused by avian-origin H7N9 in China. Luckily these viruses do not transmit efficiently in human populations. With a few amino 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 developed 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 affinity for the avian alpha 2,3-linkage receptor compared to wild type but showed no detectable increase in affinity for the human alpha 2,6-linkage receptor, using Surface Plasmon Resonance techonology. Further, the crystal structures of the VN1203mut and its complexes with either human or avian receptors demonstrate 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 crystallographic data shown here further confirm that the ability to bind the avian receptor has to decrease for a higher human receptor binding affinity. 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.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Cell Biology
研究领域[WOS]	Cell Biology
关键词[WOS]	SWINE-ORIGIN ; MAXIMUM-LIKELIHOOD ; CRYSTAL-STRUCTURE ; INFECTION ; PEPTIDES ; EPITOPES ; QUALITY ; FERRETS ; MODEL
收录类别	SCI
语种	英语
WOS记录号	WOS:000322393900004
内容类型	期刊论文
源URL	[http://124.16.173.210/handle/834782/1255]
专题	天津工业生物技术研究所_蛋白质工程与疫苗实验室高福_期刊论文
作者单位	1.China Agr Univ, Coll Vet Med, Beijing 100193, Peoples R China 2.Chinese Acad Sci, Beijing Inst Life Sci, RNIH, Beijing 100101, Peoples R China 3.Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing 100101, Peoples R China 4.Chinese Acad Sci, Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Lab Prot Engn & Vaccines, Tianjin 300308, Peoples R China 6.Chinese Ctr Dis Control & Prevent China CDC, Natl Inst Viral Dis Control & Prevent, Beijing 102206, Peoples R China
推荐引用方式 GB/T 7714	Lu, Xishan,Shi, Yi,Zhang, Wei,et al. Structure and receptor-binding properties of an airborne transmissible avian influenza A virus hemagglutinin H5 (VN1203mut)[J]. PROTEIN & CELL,2013,4(7):502-511.
APA	Lu, Xishan,Shi, Yi,Zhang, Wei,Zhang, Yanfang,Qi, Jianxun,&Gao, George F..(2013).Structure and receptor-binding properties of an airborne transmissible avian influenza A virus hemagglutinin H5 (VN1203mut).PROTEIN & CELL,4(7),502-511.
MLA	Lu, Xishan,et al."Structure and receptor-binding properties of an airborne transmissible avian influenza A virus hemagglutinin H5 (VN1203mut)".PROTEIN & CELL 4.7(2013):502-511.