Kim Jiae, Rao Venigalla B, Rao Mangala
US Military HIV Research Program, Henry M. Jackson Foundation for the Advancement of Military Medicine, 6720A Rockledge Drive, Bethesda, MD 20817, USA.
Laboratory of Adjuvant and Antigen Research, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD 20910, USA.
Vaccines (Basel). 2020 Dec 21;8(4):782. doi: 10.3390/vaccines8040782.
To prevent the spread of HIV-1, a vaccine should elicit antibodies that block viral entry for all cell types. Recently, we have developed a virus capture assay to quantitatively examine early time points of infection. Here we present data on the ability of bNAbs to inhibit capture (1 h) or replication (48 h) of purified primary acute or chronic HIV or infectious molecular clones (IMCs) in human peripheral blood mononuclear cells (PBMCs) as quantified by qRT-PCR. Although bNAbs significantly inhibited HIV-1 replication in PBMCs in a virus subtype and in a PBMC-donor specific manner, they did not inhibit virus capture of primary viruses. In contrast, IMC capture and replication in PBMCs and purified CD4 T cells were significantly inhibited by bNAbs, thus indicating that unlike IMCs, primary HIV-1 may initially bind to other cell surface molecules, which leads to virus capture even in the presence of bNAbs. Our results demonstrate that the initial interactions and some aspects of infectivity of primary HIV-1 and IMCs are inherently different, which underscores the importance of studying virus transmission using primary viruses in studies, an issue that could impact HIV-1 vaccine design strategies.
为防止HIV-1传播，疫苗应诱导产生能阻断所有细胞类型病毒进入的抗体。最近，我们开发了一种病毒捕获检测方法，用于定量检测感染的早期时间点。在此，我们展示了关于广谱中和抗体（bNAbs）抑制人外周血单核细胞（PBMCs）中纯化的原发性急性或慢性HIV或感染性分子克隆（IMCs）捕获（1小时）或复制（48小时）能力的数据，该数据通过qRT-PCR进行定量。尽管bNAbs以病毒亚型和PBMC供体特异性方式显著抑制PBMCs中的HIV-1复制，但它们并未抑制原发性病毒的病毒捕获。相比之下，bNAbs显著抑制了PBMCs和纯化的CD4 T细胞中IMCs的捕获和复制，这表明与IMCs不同，原发性HIV-1最初可能与其他细胞表面分子结合，即使在存在bNAbs的情况下也会导致病毒捕获。我们的结果表明，原发性HIV-1和IMCs的初始相互作用及感染性的某些方面存在本质差异，这突出了在研究中使用原发性病毒研究病毒传播的重要性，这一问题可能会影响HIV-1疫苗设计策略。
