Duenas-Decamp Maria José, Peters Paul J, Repik Alexander, Musich Thomas, Gonzalez-Perez Maria Paz, Caron Catherine, Brown Richard, Ball Jonathan, Clapham Paul R
Program in Molecular Medicine & Department of Molecular Genetics & Microbiology, Biotech 2, 373 Plantation Street, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Future Virol. 2010 Jul;5(4):435-451. doi: 10.2217/fvl.10.34.
HIV-1 R5 viruses predominantly use CCR5 as a coreceptor to infect CD4(+) T cells and macrophages. While R5 viruses generally infect CD4(+) T cells, research over the past few years has demonstrated that they vary extensively in their capacity to infect macrophages. Thus, R5 variants that are highly macrophage tropic have been detected in late disease and are prominent in brain tissue of subjects with neurological complications. Other R5 variants that are less sensitive to CCR5 antagonists and use CCR5 differently have also been identified in late disease. These latter variants have faster replication kinetics and may contribute to CD4 T-cell depletion. In addition, R5 viruses are highly variable in many other properties, including sensitivity to neutralizing antibodies and inhibitors that block HIV-1 entry into cells. Here, we review what is currently known about how HIV-1 R5 viruses vary in cell tropism and other properties, and discuss the implications of this variation on transmission, pathogenesis, therapy and vaccines.
HIV-1 R5病毒主要利用CCR5作为共受体来感染CD4(+) T细胞和巨噬细胞。虽然R5病毒通常感染CD4(+) T细胞，但过去几年的研究表明，它们在感染巨噬细胞的能力上差异很大。因此，在疾病晚期已检测到高度嗜巨噬细胞的R5变体，并且在有神经并发症的受试者的脑组织中很突出。在疾病晚期还发现了其他对CCR5拮抗剂不太敏感且以不同方式利用CCR5的R5变体。这些后一种变体具有更快的复制动力学，可能导致CD4 T细胞耗竭。此外，R5病毒在许多其他特性上也高度可变，包括对中和抗体和阻止HIV-1进入细胞的抑制剂的敏感性。在这里，我们综述了目前已知的HIV-1 R5病毒在细胞嗜性和其他特性方面如何变化，并讨论了这种变化对传播、发病机制、治疗和疫苗的影响。
