Vaidya Naveen K, Ribeiro Ruy M, Liu Pinghuang, Haynes Barton F, Tomaras Georgia D, Perelson Alan S
Department of Mathematics and Statistics, San Diego State University, San Diego, CA, United States.
Theoretical Biology and Biophysics Group, MS K710, Los Alamos National Laboratory, Los Alamos, NM, United States.
Front Microbiol. 2018 Jun 20;9:1326. doi: 10.3389/fmicb.2018.01326. eCollection 2018.
Recent experiments have suggested that the infectivity of simian immunodeficiency virus (SIV) and human immunodeficiency virus type-1 (HIV-1) in plasma decreases over time during primary infection. Because anti-gp41 antibodies are produced early during HIV-1 infection and form antibody-virion complexes, we studied if such early HIV-1 specific antibodies are correlated with the decay in HIV-1 infectivity. Using a viral dynamic model that allows viral infectivity to decay and frequent early viral load data obtained from 6 plasma donors we estimate that HIV-1 infectivity begins to decay after about 2 weeks of infection. The length of this delay is consistent with the time before antibody-virion complexes were detected in the plasma of these donors and is correlated ( = 0.023, = 0.87) with the time for antibodies to be first detected in plasma. Importantly, we identify that the rate of infectivity decay is significantly correlated with the rate of increase in plasma anti-gp41 IgG concentration ( = 0.046, = 0.82) and the increase in IgM+IgG anti-gp41 concentration ( = 8.37 × 10, = 0.98). Furthermore, we found that the viral load decay after the peak did not have any significant correlation with the rate of anti-gp41 IgM or IgG increase. These results indicate that early anti-gp41 antibodies may cause viral infectivity decay, but may not contribute significantly to controlling post-peak viral load, likely due to insufficient quantity or affinity. Our findings may be helpful to devise strategies, including antibody-based vaccines, to control acute HIV-1 infection.
近期实验表明,在初次感染期间,猿猴免疫缺陷病毒(SIV)和人类免疫缺陷病毒1型(HIV-1)在血浆中的传染性会随时间下降。由于抗gp41抗体在HIV-1感染早期产生并形成抗体-病毒体复合物,我们研究了这种早期的HIV-1特异性抗体是否与HIV-1传染性的下降相关。使用一个允许病毒传染性下降的病毒动力学模型,并结合从6名血浆供体获得的频繁早期病毒载量数据,我们估计HIV-1传染性在感染约2周后开始下降。这种延迟的时长与在这些供体血浆中检测到抗体-病毒体复合物之前的时间一致,并且与血浆中首次检测到抗体的时间相关(= 0.023,= 0.87)。重要的是,我们发现传染性下降速率与血浆抗gp41 IgG浓度的增加速率显著相关(= 0.046,= 0.82)以及IgM + IgG抗gp41浓度的增加(= 8.37 × 10,= 0.98)。此外,我们发现峰值后病毒载量的下降与抗gp41 IgM或IgG的增加速率没有任何显著相关性。这些结果表明,早期抗gp41抗体可能导致病毒传染性下降,但可能对控制峰值后病毒载量没有显著贡献,可能是由于数量或亲和力不足。我们的发现可能有助于制定包括基于抗体的疫苗在内的策略来控制急性HIV-1感染。