Changes in the hemagglutinin of H5N1 viruses during human infection--influence on receptor binding.
Changes in the hemagglutinin of H5N1 viruses during human infection--influence on receptor binding.
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DOI：
10.1016/j.virol.2013.08.010
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发表时间：
2013-12
期刊：
影响因子：
3.7
通讯作者：
Feizi, Ten
中科院分区：
文献类型：
--
作者：
Crusat, Martin;Liu, Junfeng;Palma, Angelina S.;Childs, Robert A.;Liu, Yan;Wharton, Stephen A.;Lin, Yi Pu;Coombs, Peter J.;Martin, Stephen R.;Matrosovich, Mikhail;Chen, Zi;Stevens, David J.;Vo Minh Hien;Tran Tan Thanh;Le Nguyen Truc Nhu;Lam Anh Nguyet;Do Quang Ha;van Doorn, H. Rogier;Tran Tinh Hien;Conradt, Harald S.;Kiso, Makoto;Gamblin, Steve J.;Chai, Wengang;Skehel, John J.;Hay, Alan J.;Farrar, Jeremy;de Jong, Menno D.;Feizi, Ten
关键词：
随着禽流感A(H5N1)病毒继续在亚洲和非洲传播，全球对即将爆发的大流行的担忧依然存在。最近的实验研究表明，目前的H5N1病毒在人与人之间的有效传播只需要几个基因变化。一个重要的步骤是改变病毒血凝素与禽类受体的优先结合，以识别存在于上呼吸道的人类受体。我们已经确定了在人类感染H5N1期间出现的受体结合变化，这是由于血凝素中的单一氨基酸替代，即Ala134Val和Ile151Phe。详细的生物学、受体结合和结构分析表明，突变病毒与禽类受体的结合减少，但与所研究的类人受体的结合没有相应增加，可能反映了一种受体结合表型，中间适应了更像人类的特征。这些观察强调，从本质上讲，禽流感H5N1病毒向有效结合人类受体的进化是一个复杂的多步骤过程。在人类感染H5N1期间，确定了HA受体结合的变化。单一的A134V和L151F替换导致与禽类受体的亲和力降低。糖链阵列分析用于确定受体结合特异性的变化。X-射线结晶学分析了受体结合改变的结构基础。
As avian influenza A(H5N1) viruses continue to circulate in Asia and Africa, global concerns of an imminent pandemic persist. Recent experimental studies suggest that efficient transmission between humans of current H5N1 viruses only requires a few genetic changes. An essential step is alteration of the virus hemagglutinin from preferential binding to avian receptors for the recognition of human receptors present in the upper airway. We have identified receptor-binding changes which emerged during H5N1 infection of humans, due to single amino acid substitutions, Ala134Val and Ile151Phe, in the hemagglutinin. Detailed biological, receptor-binding, and structural analyses revealed reduced binding of the mutated viruses to avian-like receptors, but without commensurate increased binding to the human-like receptors investigated, possibly reflecting a receptor-binding phenotype intermediate in adaptation to more human-like characteristics. These observations emphasize that evolution in nature of avian H5N1 viruses to efficient binding of human receptors is a complex multistep process. Changes in receptor binding of HA during H5N1 human infection were identified. Single A134V and L151F substitutions caused reduced affinity for avian receptors. Glycan array analyses were used to identify changes in receptor binding specificity. Structural basis for altered receptor binding was examined by X-ray crystallography.
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影响因子：
3.7
作者：
Do AH;van Doorn HR;Nghiem MN;Bryant JE;Hoang TH;Do QH;Van TL;Tran TT;Wills B;Nguyen VC;Vo MH;Vo CK;Nguyen MD;Farrar J;Tran TH;de Jong MD
通讯作者：
de Jong MD
影响因子：
3.7
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Chen LM;Blixt O;Stevens J;Lipatov AS;Davis CT;Collins BE;Cox NJ;Paulson JC;Donis RO
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Donis RO
影响因子：
158.5
作者：
de Jong, MD;Van Cam, B;Farrar, J
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Farrar, J
影响因子：
64.8
作者：
Imai, Masaki;Watanabe, Tokiko;Hatta, Masato;Das, Subash C.;Ozawa, Makoto;Shinya, Kyoko;Zhong, Gongxun;Hanson, Anthony;Katsura, Hiroaki;Watanabe, Shinji;Li, Chengjun;Kawakami, Eiryo;Yamada, Shinya;Kiso, Maki;Suzuki, Yasuo;Maher, Eileen A.;Neumann, Gabriele;Kawaoka, Yoshihiro
通讯作者：
Kawaoka, Yoshihiro
DOI：
10.1126/science.1213362
发表时间：
2012-06-22
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Herfst S;Schrauwen EJ;Linster M;Chutinimitkul S;de Wit E;Munster VJ;Sorrell EM;Bestebroer TM;Burke DF;Smith DJ;Rimmelzwaan GF;Osterhaus AD;Fouchier RA
通讯作者：
Fouchier RA