Broder C C, Collman R G
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799, USA.
J Leukoc Biol. 1997 Jul;62(1):20-9. doi: 10.1002/jlb.62.1.20.
The discovery that chemokine receptors are the human cofactors required along with CD4 for fusion and infection by HIV has opened new directions in AIDS research on mechanisms of viral entry, tropism, and pathogenesis. A possible mechanism of co-receptor function has been demonstrated that involves the formation of a complex on the cell surface between the HIV-1 envelope, CD4, and the coreceptor. Functional studies indicate that this interaction is structurally complex, that it probably involves multiple domains of the coreceptor, and that different virus isolates interact with coreceptors in distinct ways. Other immunodeficiency viruses including simian immunodeficiency virus and feline immunodeficiency virus also utilize chemokine receptors for entry. The identification of genetic polymorphisms helps explain why some people, with alterations in the CCR5 gene that prevent expression, are protected from HIV-1 infection. The discovery of specific HIV-1 fusion coreceptor molecules has not only provided new insights into the mechanisms of viral entry and tropism, but also led to new avenues of investigation on strategies to block HIV infection.
趋化因子受体是人类与CD4共同参与HIV融合和感染所需的辅助因子，这一发现为艾滋病研究中病毒进入机制、嗜性和发病机制开辟了新方向。已证实共受体功能的一种可能机制涉及HIV-1包膜、CD4和共受体在细胞表面形成复合物。功能研究表明，这种相互作用在结构上很复杂，可能涉及共受体的多个结构域，并且不同的病毒分离株以不同方式与共受体相互作用。包括猴免疫缺陷病毒和猫免疫缺陷病毒在内的其他免疫缺陷病毒也利用趋化因子受体进入细胞。基因多态性的鉴定有助于解释为什么有些人因CCR5基因改变而无法表达，从而免受HIV-1感染。特定HIV-1融合共受体分子的发现不仅为病毒进入机制和嗜性提供了新见解，还为阻断HIV感染策略的研究开辟了新途径。
