Owl monkey CCR5 reveals synergism between CD4 and CCR5 in HIV-1 entry

被引:5
|
作者
Nahabedian, John [1 ,2 ]
Sharma, Amit [1 ]
Kaczmarek, Maryska E. [3 ]
Wilkerson, Greg K. [4 ]
Sawyer, Sara L. [3 ]
Overbaugh, Julie [1 ,2 ]
机构
[1] Fred Hutchinson Canc Res Ctr, Human Biol Div, 1124 Columbia St, Seattle, WA 98104 USA
[2] Univ Washington, Pathobiol, Seattle, WA 98195 USA
[3] Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA
[4] Univ Texas MD Anderson Canc Ctr, Dept Vet Sci, Michale E Keeling Ctr Comparat Med & Res, Bastrop, TX USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
HIV-1; Receptor; Entry; CD4; CCR5; Owl monkey; Species differences; IMMUNODEFICIENCY-VIRUS TYPE-1; AMINO-TERMINUS; CELL-SURFACE; LIVING CELLS; N-TERMINUS; ENV CLONES; INFECTIONS; VARIANTS; RECEPTOR; GP120;
D O I
10.1016/j.virol.2017.09.018
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:180 / 186
页数:7
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