Carter Christoph C, Wagner Gabriel A, Hightower George K, Caballero Gemma, Phung Pham, Richman Douglas D, Pond Sergei L Kosakovsky, Smith Davey M
University of California San Diego, 9500 Gilman Dr. 0679, La Jolla, CA 92093, USA.
University of California San Diego, 9500 Gilman Dr. 0679, La Jolla, CA 92093, USA.
Virology. 2015 Jan 1;474:34-40. doi: 10.1016/j.virol.2014.10.019. Epub 2014 Nov 11.
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-naïve primary infection cohort. Using next generation sequencing (NGS), we computed sequence-based measures of diversity within HIV-1 env, gag and pol, 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.
为了更好地理解HIV特异性中和抗体（NAb）的动态变化，我们在一个特征明确、未经治疗的初发感染队列中，研究了病毒基因多样性与针对多亚型异源病毒的NAb反应之间的关联。使用下一代测序（NGS）技术，我们计算了HIV-1包膜蛋白（env）、衣壳蛋白（gag）和聚合酶蛋白（pol）基于序列的多样性指标，并将其与通过中和评分计算得出的NAb广度和效力进行比较。同期的env多样性与中和评分呈正相关（p=0.0033），中和评分与估计感染持续时间（EDI）也呈正相关（p=0.0038），env多样性与EDI同样呈正相关（p=0.0005）。早期env多样性和基线病毒载量均与未来的NAb广度和效力无关（p>0.05）。综上所述，我们队列中的中和能力不太可能取决于病毒多样性，而更有可能是env进化受NAb选择压力水平的驱动。
