Zarr Melissa, Siliciano Robert
Johns Hopkins University School of Medicine, 733 N Broadway, Room 872, Baltimore, MD 21205, USA.
Johns Hopkins University School of Medicine, 733 N Broadway, Room 872, Baltimore, MD 21205, USA; Howard Hughes Medical Institute, Baltimore, MD, USA.
Virology. 2015 Jan 1;474:1-9. doi: 10.1016/j.virol.2014.10.007. Epub 2014 Nov 7.
During HIV type 1 (HIV-1) entry, trimers of gp120 bind to CD4 and either the CCR5 or CXCR4 coreceptor on the target cell. The stoichiometric parameters associated with HIV-1 entry remain unclear. Important unanswered questions include: how many trimers must attach to CD4 molecules, how many must bind coreceptors, and how many functional gp120 subunits per trimer are required for entry? We performed single round infectivity assays with chimeric viruses and compared the experimental relative infectivity curves with curves generated by mathematical models. Our results indicate that HIV-1 entry requires only a small number of functional spikes (one or two), that Env trimers may function with fewer than three active subunits, and that there is no major difference in the stoichiometric requirements for CCR5 vs. CXCR4 mediated HIV-1 entry into host cells.
在1型人类免疫缺陷病毒（HIV-1）进入过程中，gp120三聚体与靶细胞上的CD4以及CCR5或CXCR4共受体结合。与HIV-1进入相关的化学计量参数仍不清楚。重要的未解决问题包括：多少个三聚体必须附着于CD4分子，多少个必须结合共受体，以及每个三聚体进入需要多少个功能性gp120亚基？我们用嵌合病毒进行了单轮感染性测定，并将实验相对感染性曲线与数学模型生成的曲线进行了比较。我们的结果表明，HIV-1进入仅需要少量功能性刺突（一个或两个），Env三聚体可能以少于三个活性亚基发挥作用，并且CCR5与CXCR4介导的HIV-1进入宿主细胞的化学计量要求没有重大差异。
