Nahabedian John, Sharma Amit, Kaczmarek Maryska E, Wilkerson Greg K, Sawyer Sara L, Overbaugh Julie
Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States; Pathobiology, University of Washington, Seattle, WA, United States.
Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
Virology. 2017 Dec;512:180-186. doi: 10.1016/j.virol.2017.09.018.
Studying HIV-1 replication in the presence of functionally related proteins from different species has helped define host determinants of HIV-1 infection. Humans and owl monkeys, but not macaques, encode a CD4 receptor that permits entry of transmissible HIV-1 variants due to a single residue difference. However, little is known about whether divergent CCR5 receptor proteins act as determinants of host-range. Here we show that both owl monkey (Aotus vociferans) CD4 and CCR5 receptors are functional for the entry of transmitted HIV-1 when paired with human versions of the other receptor. By contrast, the owl monkey CD4/CCR5 pair is generally a suboptimal receptor combination, although there is virus-specific variation in infection with owl monkey receptors. Introduction of the human residues 15Y and 16T within a sulfation motif into owl monkey CCR5 resulted in a gain of function. These findings suggest there is cross-talk between CD4 and CCR5 involving the sulfation motif.
研究在存在来自不同物种的功能相关蛋白的情况下HIV-1的复制，有助于确定HIV-1感染的宿主决定因素。人类和夜猴（而不是猕猴）编码一种CD4受体，由于单个残基差异，该受体允许可传播的HIV-1变体进入。然而，关于不同的CCR5受体蛋白是否作为宿主范围的决定因素，人们知之甚少。在这里，我们表明，当与人类版本的另一种受体配对时，夜猴（Aotus vociferans）的CD4和CCR5受体对于传播的HIV-1的进入都是有功能的。相比之下，夜猴的CD4/CCR5组合通常是次优的受体组合，尽管使用夜猴受体感染存在病毒特异性差异。将硫酸化基序中的人类残基15Y和16T引入夜猴CCR5导致功能增强。这些发现表明CD4和CCR5之间存在涉及硫酸化基序的相互作用。
