Seattle BioMed, Seattle, Washington, USA.
J Virol. 2012 Dec;86(23):12676-85. doi: 10.1128/JVI.01893-12. Epub 2012 Sep 12.
Approximately 1% of those infected with HIV-1 develop broad and potent serum cross-neutralizing antibody activities. It is unknown whether or not the development of such immune responses affects the replication of the contemporaneous autologous virus. Here, we defined a pathway of autologous viral escape from contemporaneous potent and broad serum neutralizing antibodies developed by an elite HIV-1-positive (HIV-1(+)) neutralizer. These antibodies potently neutralize diverse isolates from different clades and target primarily the CD4-binding site (CD4-BS) of the viral envelope glycoprotein. Viral escape required mutations in the viral envelope glycoprotein which limited the accessibility of the CD4-binding site to the autologous broadly neutralizing anti-CD4-BS antibodies but which allowed the virus to infect cells by utilizing CD4 receptors on their surface. The acquisition of neutralization resistance, however, resulted in reduced cell entry potential and slower viral replication kinetics. Our results indicate that in vivo escape from autologous broadly neutralizing antibodies exacts fitness costs to HIV-1.
约 1%感染 HIV-1 的人会产生广泛而有效的血清交叉中和抗体活性。目前尚不清楚这种免疫反应的发展是否会影响同时存在的自体病毒的复制。在这里，我们定义了一种自体病毒逃避同时存在的高效广谱血清中和抗体的途径，这些抗体能有效中和来自不同进化枝的多种分离株，主要针对病毒包膜糖蛋白的 CD4 结合位点（CD4-BS）。病毒逃逸需要病毒包膜糖蛋白发生突变，这些突变限制了自体广谱中和抗 CD4-BS 抗体对 CD4 结合位点的可及性，但允许病毒通过其表面的 CD4 受体感染细胞。然而，获得中和抗性会导致细胞进入能力降低和病毒复制动力学减慢。我们的结果表明，HIV-1 从自体广谱中和抗体中逃逸会产生适应性成本。
