Kim Jiae, Jobe Ousman, Peachman Kristina K, Michael Nelson L, Robb Merlin L, Rao Mangala, Rao Venigalla B
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 20910, MD, USA.
US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring 20910, MD, USA.
Virology. 2017 Aug;508:188-198. doi: 10.1016/j.virol.2017.05.015. Epub 2017 May 31.
Development of vaccines capable of eliciting broadly neutralizing antibodies (bNAbs) is a key goal to controlling the global AIDS epidemic. To be effective, bNAbs must block the capture of HIV-1 to prevent viral acquisition and establishment of reservoirs. However, the role of bNAbs, particularly during initial exposure of primary viruses to host cells, has not been fully examined. Using a sensitive, quantitative, and high-throughput qRT-PCR assay, we found that primary viruses were captured by host cells and converted into a trypsin-resistant form in less than five minutes. We discovered, unexpectedly, that bNAbs did not block primary virus capture, although they inhibited the capture of pseudoviruses/IMCs and production of progeny viruses at 48h. Further, viruses escaped bNAb inhibition unless the bNAbs were present in the initial minutes of exposure of virus to host cells. These findings will have important implications for HIV-1 vaccine design and determination of vaccine efficacy.
开发能够引发广泛中和抗体（bNAbs）的疫苗是控制全球艾滋病流行的关键目标。为了有效，bNAbs必须阻断HIV-1的捕获以防止病毒感染和储存库的建立。然而，bNAbs的作用，特别是在原发性病毒初次暴露于宿主细胞期间，尚未得到充分研究。使用灵敏、定量且高通量的qRT-PCR检测方法，我们发现原发性病毒在不到五分钟的时间内被宿主细胞捕获并转化为胰蛋白酶抗性形式。出乎意料的是，我们发现bNAbs虽然在48小时时抑制了假病毒/整合膜蛋白复合体（IMCs）的捕获和子代病毒的产生，但并未阻断原发性病毒的捕获。此外，除非在病毒暴露于宿主细胞的最初几分钟内就存在bNAbs，否则病毒会逃脱bNAb的抑制作用。这些发现将对HIV-1疫苗设计和疫苗效力的测定产生重要影响。
