Tachibana Shingo, Sasaki Maho, Tanaka Takako, Inoue Mari, Ophinni Youdiil, Kotaki Tomohiro, Kameoka Masanori
1 Department of International Health, Kobe University Graduate School of Health Sciences, Kobe University , Kobe, Japan .
2 Medical Technology Major, Kobe University School of Medicine Faculty of Health Sciences, School of Medicine, Kobe University , Kobe, Japan .
AIDS Res Hum Retroviruses. 2017 Dec;33(12):1248-1257. doi: 10.1089/aid.2017.0063. Epub 2017 Oct 17.
The envelope glycoprotein (Env) gp120 of human immunodeficiency virus type 1 (HIV-1) plays a critical role in viral entry into host cells. The broadly neutralizing human monoclonal antibody VRC01, which recognizes the CD4 binding site on gp120, neutralizes more than 90% of HIV-1 isolates. However, some of the CRF01_AE viruses prevalent in Southeast Asia are resistant to VRC01-mediated neutralization. We previously reported that 3 amino acid residues at positions 185, 186, and 197 of gp120 played an important role in the VRC01 resistance of CRF01_AE Env (AE-Env) clones isolated from HIV-infected Thai individuals. However, the VRC01 susceptibility of AE-Env clones was not fully explained by mutations at these 3 residues. In the present study, we examined other factors involved in the acquisition of viral VRC01 resistance. Neutralization tests using lentiviral vectors expressing a series of mutant AE-Env clones revealed that the deletion of 2-4 amino acid residues on the loop structure in the V5 region of gp120 conferred VRC01 resistance to several AE-Env clones. Our results provide novel insights into the mechanisms underlying viral VRC01 resistance.
1型人类免疫缺陷病毒（HIV-1）的包膜糖蛋白（Env）gp120在病毒进入宿主细胞的过程中起着关键作用。广泛中和的人类单克隆抗体VRC01可识别gp120上的CD4结合位点，能中和超过90%的HIV-1分离株。然而，东南亚流行的一些CRF01_AE病毒对VRC01介导的中和作用具有抗性。我们之前报道过，gp120第185、186和197位的3个氨基酸残基在从感染HIV的泰国个体中分离出的CRF01_AE Env（AE-Env）克隆对VRC01的抗性中起重要作用。然而，这3个残基的突变并不能完全解释AE-Env克隆对VRC01的敏感性。在本研究中，我们检测了与病毒获得VRC01抗性有关的其他因素。使用表达一系列突变AE-Env克隆的慢病毒载体进行的中和试验表明，gp120的V5区域环结构上2至4个氨基酸残基的缺失赋予了几个AE-Env克隆对VRC01的抗性。我们的结果为病毒VRC01抗性的潜在机制提供了新的见解。
