Stantchev T S, Broder C C
Department of Microbiology and Immunology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814-4799, USA.
Cytokine Growth Factor Rev. 2001 Jun-Sep;12(2-3):219-43. doi: 10.1016/s1359-6101(00)00033-2.
The chemokines and their receptors have been receiving exceptional attention in recent years following the discoveries that some chemokines could specifically block human immunodeficiency virus type 1 (HIV-1) infection and that certain chemokine receptors were the long-sought coreceptors which, along with CD4, are required for the productive entry of HIV-1 and HIV-2 isolates. Several chemokine receptors or orphan chemokine receptor-like molecules can support the entry of various viral strains, but the clinical significance of the CXCR4 and CCR5 coreceptors appear to overshadow a critical role for any of the other coreceptors and all HIV-1 and HIV-2 strains best employ one or both of these coreceptors. Binding of the HIV-1 envelope glycoprotein gp120 subunit to CD4 and/or an appropriate chemokine receptor triggers conformational changes in the envelope glycoprotein oligomer that allow it to facilitate the fusion of the viral and host cell membranes. During these interactions, gp120 appears to be capable of inducing a variety of signaling events, all of which are still not defined in detail. In addition, the more recently observed dichotomous effects, of both inhibition and enhancement, that chemokines and their receptor signaling events elicit on the HIV-1 entry and replication processes has once again highlighted the intricate and complex balance of factors that govern the pathogenic process. Here, we will review and discuss these new observations summarizing the potential significance these processes may have in HIV-1 infection. Understanding the complexities and significance of the signaling processes that the chemokines and viral products induce may substantially enhance our understanding of HIV-1 pathogenesis, and perhaps facilitate the discovery of new ways for the prevention and treatment of HIV-1 disease.
近年来，趋化因子及其受体受到了格外关注，这是因为发现某些趋化因子能够特异性阻断1型人类免疫缺陷病毒（HIV-1）感染，且某些趋化因子受体是长期以来一直在寻找的共受体，它们与CD4一起，是HIV-1和HIV-2毒株有效进入细胞所必需的。几种趋化因子受体或类孤儿趋化因子受体分子能够支持各种病毒毒株的进入，但CXCR4和CCR5共受体的临床意义似乎盖过了其他任何共受体的关键作用，并且所有HIV-1和HIV-2毒株最好利用这两种共受体中的一种或两种。HIV-1包膜糖蛋白gp120亚基与CD4和/或适当的趋化因子受体结合，会触发包膜糖蛋白寡聚体的构象变化，使其能够促进病毒膜与宿主细胞膜的融合。在这些相互作用过程中，gp120似乎能够诱导多种信号事件，所有这些事件仍未得到详细界定。此外，最近观察到趋化因子及其受体信号事件对HIV-1进入和复制过程产生的抑制和增强的二分效应，再次凸显了控制致病过程的各种因素之间复杂而微妙的平衡。在此，我们将回顾和讨论这些新观察结果，总结这些过程在HIV-1感染中可能具有的潜在意义。了解趋化因子和病毒产物诱导的信号过程的复杂性和意义，可能会极大地增进我们对HIV-1发病机制的理解，并可能有助于发现预防和治疗HIV-1疾病的新方法。
