Bieniasz P D, Cullen B R
Department of Genetics and Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA.
Front Biosci. 1998 Jan 1;3:d44-58. doi: 10.2741/a265.
Primate lentiviruses infect target cells by interacting with the cell surface protein, CD4 and additional molecules, termed coreceptors. Recently, HIV-1 coreceptors have been identified as seven transmembrane spanning, G-protein coupled receptors of the chemokine receptor family. Thus, expression of CD4 and an appropriate coreceptor is both necessary and sufficient to render target cell permissive for fusion with virions or infected cells. The spectrum of tissue tropisms exhibited by primate lentiviruses can be largely explained by differential utilization and distribution of coreceptors. This article reviews what is currently known about the selective utilization of particular coreceptors by primate lentiviruses and the nature of the envelope/coreceptor interaction, with particular reference to two important HIV-1 coreceptors, CCR-5 and CXCR-4. It has become clear that these interactions are somewhat 'plastic': Variability is evident, both in the selection of coreceptor and the way in which different viral strains interact with their cognate coreceptors. The implications of these findings both for attempts to block HIV infection with coreceptor targeted agents and for understanding HIV replication in vivo is discussed.
灵长类慢病毒通过与细胞表面蛋白CD4及其他被称为共受体的分子相互作用来感染靶细胞。最近，HIV-1共受体已被鉴定为趋化因子受体家族中具有七个跨膜结构域的G蛋白偶联受体。因此，CD4和合适的共受体的表达对于使靶细胞能够与病毒粒子或感染细胞融合而言既是必要的也是充分的。灵长类慢病毒所表现出的组织嗜性谱在很大程度上可以通过共受体的差异利用和分布来解释。本文综述了目前关于灵长类慢病毒对特定共受体的选择性利用以及包膜/共受体相互作用性质的了解，特别提及了两种重要的HIV-1共受体CCR-5和CXCR-4。已经清楚的是，这些相互作用在某种程度上是“可塑性的”：在共受体的选择以及不同病毒株与其同源共受体相互作用的方式上都存在明显的变异性。本文讨论了这些发现对于用共受体靶向药物阻断HIV感染的尝试以及理解HIV在体内复制的意义。
