The presence of glutamine at position 315 but not epitope masking predominantly hinders HIV subtype C neutralization by the anti-V3 antibody B4e8.
The presence of glutamine at position 315 but not epitope masking predominantly hinders HIV subtype C neutralization by the anti-V3 antibody B4e8.
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DOI：
10.1016/j.virol.2014.05.034
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发表时间：
2014-08
期刊：
影响因子：
3.7
通讯作者：
Pantophlet, Ralph
中科院分区：
文献类型：
--
作者：
Manhas, Savrina;Chau, Dennis;Rempel, Caitlin;Clark, Brenda E.;Auyeung, Kate;Pantophlet, Ralph
抗体B4e8表现出适度的交叉中和活性，对HIV B亚型有选择性，这可能是由于B4e8‘S与Arg315广泛相互作用所致，Arg315位于大多数B亚型V3序列的中心，但在C亚型中被Gln取代。目前尚不清楚Gln315和/或其他因素(如表位掩蔽)在多大程度上阻碍了B4e8’S中和C亚型毒株的能力。我们在这里证实，在B亚型病毒中，Arg315到Gln的替换取消了B4e8的中和活性。相反，耐B4e8的C亚型病毒对Gln到Arg的替换变得敏感。B4e8敏感和耐药C亚型菌株之间的V2区域交换揭示了V2在限制B4e8访问方面的作用，但这不如Arg315的缺失那么显著。我们的发现，虽然说明了Arg315对B4e8的重要性，但也表明一些C亚型毒株可能容易受到B4e8衍生物的影响，这些衍生品能够与含有Gln315的序列结合得更强。
Antibody B4e8 exhibits modest cross-neutralizing activity, with preference for HIV subtype B. This preference might be explained by B4e8’s extensive interaction with Arg315, which occurs at the center of most subtype B V3 sequences but is replaced by Gln in subtype C. The extent to which B4e8’s ability to neutralize subtype C strains is hindered by Gln315 and/or other factors, e.g. epitope masking, is unclear. We confirmed here that an Arg315-to-Gln substitution in a subtype B virus abrogates B4e8 neutralizing activity. Conversely, B4e8-resistant subtype C viruses were rendered sensitive upon Gln-to-Arg substitution. V2 region swapping between B4e8-sensitive and- resistant subtype C strains revealed a role for V2 in limiting B4e8 access, but this was less significant than the absence of Arg315. Our findings, while illustrating the importance of Arg315 for B4e8, suggest that some subtype C strains may be vulnerable to B4e8 derivatives capable of binding stronger to Gln315-containing sequences.
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DOI：
10.1126/science.1213782
发表时间：
2011-12-02
期刊：
Science (New York, N.Y.)
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