Betacoronavirus Adaptation to Humans Involved Progressive Loss of Hemagglutinin-Esterase Lectin Activity

被引:100
作者
Bakkers, Mark J. G. [1 ]
Lang, Yifei [1 ]
Feitsma, Louris J.
Hulswit, Ruben J. G. [1 ]
de Poot, Stefanie A. H. [1 ]
van Vliet, Arno L. W. [1 ]
Margine, Irina [1 ]
de Groot-Mijnes, Jolanda D. F. [3 ]
van Kuppeveld, Frank J. M. [1 ]
Langereis, Martijn A. [1 ]
Huizinga, Eric G. [2 ]
de Groot, Raoul J. [1 ]
机构
[1] Univ Utrecht, Div Virol, Dept Infect Dis & Immunol, Fac Vet Med, NL-3584 CH Utrecht, Netherlands
[2] Univ Utrecht, Crystal & Struct Chem, Bijvoet Ctr Biomol Res, Fac Sci, NL-3584 CH Utrecht, Netherlands
[3] Univ Med Ctr Utrecht, Dept Med Microbiol, NL-3584 CX Utrecht, Netherlands
关键词
HUMAN CORONAVIRUS OC43; INFLUENZA-VIRUS NEURAMINIDASE; ACETYLATED SIALIC-ACID; SPIKE PROTEIN; STALK LENGTH; BINDING-SITE; TRANSMISSION; EVOLUTION; HKU1; RECOMBINATION;
D O I
10.1016/j.chom.2017.02.008
中图分类号
Q93 [微生物学];
学科分类号
071005 [微生物学];
摘要
Human beta1-coronavirus (beta 1CoV) OC43 emerged relatively recently through a single zoonotic introduction. Like relatedanimal beta 1CoVs, OC43 uses 9-O-acetylated sialic acid as receptor determinant. b1CoV receptor binding is typically controlled by attachment/fusion spike protein S and receptor-binding/receptor-destroying hemagglutinin-esterase protein HE. We show that following OC43's introduction into humans, HE-mediated receptor binding was selected against and ultimately lost through progressive accumulation ofmutations in the HE lectin domain. Consequently, virion-associated receptor-destroying activity toward multivalent glycoconjugates was reduced and altered such that some clustered receptor populations are no longer cleaved. Loss of HE lectin function was also observed for another respiratory human coronavirus, HKU1. This thus appears to be an adaptation to the sialoglycome of the human respiratory tract and for replication in human airways. The findings suggest that the dynamics of virion-glycan interactions contribute to host tropism. Our observations are relevant also to other human respiratory viruses of zoonotic origin, particularly influenza A virus.
引用
收藏
页码:356 / 366
页数:11
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