How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin.
How single mutations affect viral escape from broad and narrow antibodies to H1 influenza hemagglutinin.
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DOI：
10.1038/s41467-018-03665-3
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发表时间：
2018-04-11
影响因子：
16.6
通讯作者：
Bloom JD
中科院分区：
文献类型：
--
作者：
Doud MB;Lee JM;Bloom JD
流感病毒可以通过单一突变逃脱大多数抗体。然而，罕见的抗体可以广泛中和许多病毒株。目前尚不清楚，如果有强大的压力，流感病毒逃脱这种抗体的难度有多大。在这里，我们绘制了所有单一氨基酸突变，这些突变增加了对H1血凝素广泛抗体的抵抗力。我们的方法不仅识别抗原突变，而且量化它们的影响大小。所有抗体都选择突变，但效果大小差别很大。这种病毒可以逃脱血凝素受体结合部位的广泛抗体，就像它逃避狭隘的毒株特异性抗体一样：通过具有巨大影响的单一突变。相比之下，针对血凝素茎的广泛抗体只选择影响很小的突变。因此，在我们研究的抗体中，广度并不是通过单一突变逃脱病毒的可能性的完美指标。与这里测试的其他抗体相比，针对H1血凝素茎的抗体更难逃脱。甲型流感病毒可以逃脱抗体，但目前尚不清楚逃逸的难易程度如何取决于抗体所针对的表位。在这里，作者们表明，中和广度不是单一突变容易逃脱病毒的一个不完美的指标，而针对血凝素茎的抗体更难逃脱。
Influenza virus can escape most antibodies with single mutations. However, rare antibodies broadly neutralize many viral strains. It is unclear how easily influenza virus might escape such antibodies if there was strong pressure to do so. Here, we map all single amino-acid mutations that increase resistance to broad antibodies to H1 hemagglutinin. Our approach not only identifies antigenic mutations but also quantifies their effect sizes. All antibodies select mutations, but the effect sizes vary widely. The virus can escape a broad antibody to hemagglutinin’s receptor-binding site the same way it escapes narrow strain-specific antibodies: via single mutations with huge effects. In contrast, broad antibodies to hemagglutinin’s stalk only select mutations with small effects. Therefore, among the antibodies we examine, breadth is an imperfect indicator of the potential for viral escape via single mutations. Antibodies targeting the H1 hemagglutinin stalk are quantifiably harder to escape than the other antibodies tested here. Influenza A virus can escape antibodies, but it is unclear how the ease of escape depends on the epitope targeted by an antibody. Here, the authors show that neutralization breadth is an imperfect indicator of the ease of viral escape by single mutations, and that antibodies targeting the stalk of hemagglutinin are harder to escape.
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影响因子：
6.7
作者：
Doud, Michael B.;Hensley, Scott E.;Bloom, Jesse D.
通讯作者：
Bloom, Jesse D.
影响因子：
56.9
作者：
DIAMOND, DC;JAMESON, BA;WIMMER, E
通讯作者：
WIMMER, E
影响因子：
17.1
作者：
Andrews SF;Huang Y;Kaur K;Popova LI;Ho IY;Pauli NT;Henry Dunand CJ;Taylor WM;Lim S;Huang M;Qu X;Lee JH;Salgado-Ferrer M;Krammer F;Palese P;Wrammert J;Ahmed R;Wilson PC
通讯作者：
Wilson PC
DOI：
10.1073/pnas.1323502111
发表时间：
2014-09-02
影响因子：
11.1
作者：
Drexler, Jan Felix;Grard, Gilda;Drosten, Christian
通讯作者：
Drosten, Christian
影响因子：
10.7
作者：
Bloom, Jesse D.
通讯作者：
Bloom, Jesse D.