Predicting the antigenic structure of the pandemic (H1N1) 2009 influenza virus hemagglutinin.
Predicting the antigenic structure of the pandemic (H1N1) 2009 influenza virus hemagglutinin.
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DOI：
10.1371/journal.pone.0008553
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发表时间：
2010-01-01
期刊：
影响因子：
3.7
通讯作者：
Takada A
中科院分区：
文献类型：
--
作者：
Igarashi M;Ito K;Yoshida R;Tomabechi D;Kida H;Takada A
大流行性流感病毒（2009 H1N1）最近传入人群。2009年H1N1流感的血凝素（HA）基因来源于“经典猪H1N1”病毒，这种病毒可能与1918年引起大流行的人类H1N1病毒有共同的祖先，后者的后代病毒仍然在人群中传播，HA的抗原性发生了高度改变。然而，在结构基础上比较2009 H1N1、1918年大流行和季节性人类H1N1病毒的HA抗原性的信息一直缺乏。通过HA结构的同源性建模，我们发现2009 H1N1和1918大流行病毒的HA在已知抗原位点上具有大量的氨基酸残基，这表明存在共同的表位来中和对这两种HA交叉反应的抗体。有人指出，20世纪30年代至40年代分离的早期人类H1N1病毒仍然含有一些在2009年H1N1中也发现的原始表位。有趣的是，虽然2009 H1N1 HA缺乏与人类H1N1病毒早期流行期间抗原变化相关的多个n -糖基化，但2009 H1N1 HA仍然保留独特的三个密码子基序，其中一些基序通过人类H1N1病毒的单核苷酸突变成为n -糖基化位点。因此，我们假设涉及保守氨基酸的2009 H1N1 HA抗原位点将很快被人类抗体介导的选择压力靶向。事实上，这里预测的氨基酸替换正在最近的2009 H1N1变种中发生。本研究提示，1918年大流行病毒或其早期后代病毒自然感染引发的抗体在对2009年H1N1的特异性免疫中发挥作用，并为2009年H1N1在人群中进化过程中未来可能发生的抗原变化提供了见解。
The pandemic influenza virus (2009 H1N1) was recently introduced into the human population. The hemagglutinin (HA) gene of 2009 H1N1 is derived from “classical swine H1N1” virus, which likely shares a common ancestor with the human H1N1 virus that caused the pandemic in 1918, whose descendant viruses are still circulating in the human population with highly altered antigenicity of HA. However, information on the structural basis to compare the HA antigenicity among 2009 H1N1, the 1918 pandemic, and seasonal human H1N1 viruses has been lacking. By homology modeling of the HA structure, here we show that HAs of 2009 H1N1 and the 1918 pandemic virus share a significant number of amino acid residues in known antigenic sites, suggesting the existence of common epitopes for neutralizing antibodies cross-reactive to both HAs. It was noted that the early human H1N1 viruses isolated in the 1930s–1940s still harbored some of the original epitopes that are also found in 2009 H1N1. Interestingly, while 2009 H1N1 HA lacks the multiple N-glycosylations that have been found to be associated with an antigenic change of the human H1N1 virus during the early epidemic of this virus, 2009 H1N1 HA still retains unique three-codon motifs, some of which became N-glycosylation sites via a single nucleotide mutation in the human H1N1 virus. We thus hypothesize that the 2009 H1N1 HA antigenic sites involving the conserved amino acids will soon be targeted by antibody-mediated selection pressure in humans. Indeed, amino acid substitutions predicted here are occurring in the recent 2009 H1N1 variants. The present study suggests that antibodies elicited by natural infection with the 1918 pandemic or its early descendant viruses play a role in specific immunity against 2009 H1N1, and provides an insight into future likely antigenic changes in the evolutionary process of 2009 H1N1 in the human population.
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影响因子：
14.9
作者：
Eswar, N;John, B;Sali, A
通讯作者：
Sali, A
影响因子：
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作者：
SHEERAR, MG;EASTERDAY, BC;HINSHAW, VS
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HINSHAW, VS
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作者：
Taubenberger, JK;Reid, AH;Fanning, TG
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Fanning, TG
DOI：
10.1098/rstb.2001.0979
发表时间：
2001-12-29
期刊：
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES
影响因子：
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作者：
Schickli, JH;Flandorfer, A;Palese, P
通讯作者：
Palese, P
影响因子：
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作者：
CATON, AJ;BROWNLEE, GG;GERHARD, W
通讯作者：
GERHARD, W