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

2017; Elsevier BV; Volume: 512; Linguagem: Inglês

10.1016/j.virol.2017.09.018

1096-0341

John F. Nahabedian, Amit Sharma, Maryska E. Kaczmarek, Greg K. Wilkerson, Sara L. Sawyer, Julie Overbaugh,

T-cell and B-cell Immunology

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.