Universal anti-neuraminidase antibody inhibiting all influenza A subtypes
Universal anti-neuraminidase antibody inhibiting all influenza A subtypes
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DOI：
10.1016/j.antiviral.2013.09.018
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发表时间：
2013-11-01
影响因子：
7.6
通讯作者：
Li, Xuguang
中科院分区：
文献类型：
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作者：
Doyle, Tracey M.;Hashem, Anwar M.;Li, Xuguang
所有甲型流感病毒神经氨酸酶（NA）中唯一普遍保守的序列位于氨基酸222-230之间，并且在病毒复制中起关键作用。然而，尚不清楚该通用表位是否在感染过程中暴露以允许抗体结合和抑制。使用单克隆抗体（MAb）针对这个特定的表位，我们证明了所有九种亚型的NA抑制在体外的MAb。此外，该抗体还在用致死剂量的小鼠适应性H1N1和H3 N2（分别代表I组和II组病毒）攻击的小鼠中提供异亚型保护。此外，我们报告了位于活性位点附近的氨基酸残基1222和E227对于该抗体的抑制是不可或缺的。这种独特的，高度保守的线性序列在病毒NA可能是一个有吸引力的免疫保护针对不同的流感病毒株的目标。皇冠版权所有（C）2013由爱思唯尔B. V.出版保留所有权利。
The only universally conserved sequence amongst all influenza A viral neuraminidase (NA) is located between amino acids 222-230 and plays crucial roles in viral replication. However, it remained unclear as to whether this universal epitope is exposed during the course of infection to allow binding and inhibition by antibodies. Using a monoclonal antibody (MAb) targeting this specific epitope, we demonstrated that all nine subtypes of NA were inhibited in vitro by the MAb. Moreover, the antibody also provided heterosubtypic protection in mice challenged with lethal doses of mouse-adapted H1N1 and H3N2, which represent group I and II viruses, respectively. Furthermore, we report amino acid residues 1222 and E227, located in close proximity to the active site, are indispensable for inhibition by this antibody. This unique, highly-conserved linear sequence in viral NA could be an attractive immunological target for protection against diverse strains of influenza viruses. Crown Copyright (C) 2013 Published by Elsevier B.V. All rights reserved.