HIV-1 neutralizing antibody response and viral genetic diversity characterized with next generation sequencing

被引：19

作者：

Carter, Christoph C. ^{[1
]}

Wagner, Gabriel A. ^{[1
]}

Hightower, George K. ^{[1
]}

Caballero, Gemma ^{[2
]}

Phung, Pham ^{[3
]}

Richman, Douglas D. ^{[1
,2
]}

Pond, Sergei L. Kosakovsky ^{[1
]}

Smith, Davey M. ^{[1
,2
]}

机构：

[1] Univ Calif San Diego, La Jolla, CA 92093 USA

[2] Vet Affairs San Diego Healthcare Syst, San Diego, CA USA

[3] Monogram Biosci Inc, San Francisco, CA USA

来源：

VIROLOGY | 2015年 / 474卷

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

HIV-1 genetic diversity; Neutralizing antibody; Next generation sequencing; Neutralizing antibody breadth and potency; Viral evolution; IMMUNODEFICIENCY-VIRUS TYPE-1; DUAL INFECTION; EVOLUTION; THERAPY; ESCAPE; TRANSMISSION; VARIANTS; BREADTH; BROAD; SERA;

D O I：

10.1016/j.virol.2014.10.019

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

To better understand the dynamics of HIV-specific neutralizing antibody (NAb), we examined associations between viral genetic diversity and the NAb response against a multi-subtype panel of heterologous viruses in a well-characterized, therapy-naive primary infection cohort. Using next generation sequencing (NGS), we computed sequence-based measures of diversity within HIV-1 env, gag and pal, and compared them to NAb breadth and potency as calculated by a neutralization score. Contemporaneous env diversity and the neutralization score were positively correlated (p=0.0033), as were the neutralization score and estimated duration of infection (EDI) (p=0.0038), and env diversity and EDI (p=0.0005). Neither early env diversity nor baseline viral load correlated with future NAb breadth and potency (p > 0.05). Taken together, it is unlikely that neutralizing capability in our cohort was conditioned on viral diversity, but rather that env evolution was driven by the level of NAb selective pressure. (C) 2014 Elsevier Inc. All rights reserved.

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页码：34 / 40

页数：7

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