A single base-pair change in 2009 H1N1 hemagglutinin increases human receptor affinity and leads to efficient airborne viral transmission in ferrets.
A single base-pair change in 2009 H1N1 hemagglutinin increases human receptor affinity and leads to efficient airborne viral transmission in ferrets.
复制标题
DOI：
10.1371/journal.pone.0017616
复制
发表时间：
2011-03-02
期刊：
影响因子：
3.7
通讯作者：
Sasisekharan R
中科院分区：
文献类型：
--
作者：
Jayaraman A;Pappas C;Raman R;Belser JA;Viswanathan K;Shriver Z;Tumpey TM;Sasisekharan R
2009年H1N1甲型流感病毒作为主要的H1N1亚型继续在人群中传播。流行病学研究和使用雪貂模型的空气传播研究表明，2009年H1N1病毒的传播效率低于以前的季节性毒株和1918年H1N1大流行毒株。我们最近将这种降低的传输效率与2009年H1N1血凝素（HA）与α2→6唾液酸化聚糖受体（人类受体）的结合亲和力降低相关联。在此，我们报告了2009年H1N1甲型流感病毒A/加州/04/09或CA 04/09的代表性聚糖受体结合位点（RBS）中的单点突变（Ile 219 →Lys;碱基对变化），定量增加了其与人受体的结合亲和力。增加的人受体亲和力与来自高传播性季节性和1918年大流行性H1N1病毒的HA的亲和力在相同范围内。此外，在RBS中携带这种突变的2009 H1N1病毒（使用反向遗传学产生）通过呼吸道飞沫在雪貂中有效传播，从而重新建立了我们先前观察到的人类受体结合亲和力和传播效率之间的相关性。这些发现对于监测目前流行的2009年H1N1病毒的演变具有重要意义。
The 2009 H1N1 influenza A virus continues to circulate among the human population as the predominant H1N1 subtype. Epidemiological studies and airborne transmission studies using the ferret model have shown that the transmission efficiency of 2009 H1N1 viruses is lower than that of previous seasonal strains and the 1918 pandemic H1N1 strain. We recently correlated this reduced transmission efficiency to the lower binding affinity of the 2009 H1N1 hemagglutinin (HA) to α2→6 sialylated glycan receptors (human receptors). Here we report that a single point mutation (Ile219→Lys; a base pair change) in the glycan receptor-binding site (RBS) of a representative 2009 H1N1 influenza A virus, A/California/04/09 or CA04/09, quantitatively increases its human receptor-binding affinity. The increased human receptor-affinity is in the same range as that of the HA from highly transmissible seasonal and 1918 pandemic H1N1 viruses. Moreover, a 2009 H1N1 virus carrying this mutation in the RBS (generated using reverse genetics) transmits efficiently in ferrets by respiratory droplets thereby reestablishing our previously observed correlation between human receptor-binding affinity and transmission efficiency. These findings are significant in the context of monitoring the evolution of the currently circulating 2009 H1N1 viruses.
登录
查看更多内容
DOI：
10.1056/nejmoa0905498
发表时间：
2009-12-31
期刊：
The New England journal of medicine
影响因子：
--
作者：
Cauchemez S;Donnelly CA;Reed C;Ghani AC;Fraser C;Kent CK;Finelli L;Ferguson NM
通讯作者：
Ferguson NM
影响因子：
6.4
作者：
Morens, David M.;Taubenberger, Jeffery K.;Fauci, Anthony S.
通讯作者：
Fauci, Anthony S.
影响因子：
64.8
作者：
Neumann, Gabriele;Noda, Takeshi;Kawaoka, Yoshihiro
通讯作者：
Kawaoka, Yoshihiro
影响因子：
56.9
作者：
Tumpey, Terrence M.;Maines, Taronna R.;Garcia-Sastre, Adolfo
通讯作者：
Garcia-Sastre, Adolfo
影响因子：
5.4
作者：
Hai, Rong;Martinez-Sobrido, Luis;Palese, Peter
通讯作者：
Palese, Peter