Farzan M, Choe H, Martin K A, Sun Y, Sidelko M, Mackay C R, Gerard N P, Sodroski J, Gerard C
Division of Human Retrovirology, Dana-Farber Cancer Institute, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Biol Chem. 1997 Mar 14;272(11):6854-7. doi: 10.1074/jbc.272.11.6854.
The human immunodeficiency virus type 1 (HIV-1) requires the presence of specific chemokine receptors in addition to CD4 to enter its target cell. The chemokine receptor CCR5 is used by macrophage-tropic strains of HIV-1, which predominate during the asymptomatic stages of infection. Here we investigate whether the ability of CCR5 to signal in response to its beta-chemokine ligands is necessary or sufficient for viral entry. Three CCR5 mutants with little or no ability to mobilize calcium in response to macrophage inflammatory protein-1beta could nonetheless support HIV-1 entry and the early steps in the virus life cycle with efficiencies comparable with those of wild-type CCR5. Conversely, a chimeric receptor with the N terminus of CCR2 replacing that of CCR5 responded to macrophage inflammatory protein-1beta and MCP-1 but did not efficiently support viral entry. These results demonstrate that chemokine signaling and HIV-1 entry are separable functions of CCR5 and that only viral entry requires the N-terminal domain of CCR5.
1型人类免疫缺陷病毒（HIV-1）除了需要CD4外，还需要特定趋化因子受体的存在才能进入其靶细胞。HIV-1的巨噬细胞嗜性毒株利用趋化因子受体CCR5，这些毒株在感染的无症状阶段占主导地位。在此，我们研究CCR5响应其β趋化因子配体而发出信号的能力对于病毒进入是否必要或充分。三个几乎没有或完全没有能力响应巨噬细胞炎性蛋白-1β而动员钙离子的CCR5突变体，仍然能够支持HIV-1进入以及病毒生命周期的早期步骤，其效率与野生型CCR5相当。相反，一个用CCR2的N末端替换CCR5的N末端的嵌合受体对巨噬细胞炎性蛋白-1β和MCP-1有反应，但不能有效地支持病毒进入。这些结果表明，趋化因子信号传导和HIV-1进入是CCR5的可分离功能，并且只有病毒进入需要CCR5的N末端结构域。
