Tat对CXCR4的选择性拮抗作用：对HIV-1体内共受体使用扩展的影响。
Selective CXCR4 antagonism by Tat: implications for in vivo expansion of coreceptor use by HIV-1.
作者信息
Xiao H, Neuveut C, Tiffany H L, Benkirane M, Rich E A, Murphy P M, Jeang K T
机构信息
Laboratories of Molecular Microbiology and Host Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892-0460, USA.
出版信息
Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11466-71. doi: 10.1073/pnas.97.21.11466.
Chemokines and chemokine receptors play important roles in HIV-1 infection and tropism. CCR5 is the major macrophage-tropic coreceptor for HIV-1 whereas CXC chemokine receptor 4 (CXCR4) serves the counterpart function for T cell-tropic viruses. An outstanding biological mystery is why only R5-HIV-1 is initially detected in new seroconvertors who are exposed to R5 and X4 viruses. Indeed, X4 virus emerges in a minority of patients and only in the late stage of disease, suggesting that early negative selection against HIV-1-CXCR4 interaction may exist. Here, we report that the HIV-1 Tat protein, which is secreted from virus-infected cells, is a CXCR4-specific antagonist. Soluble Tat selectively inhibited the entry and replication of X4, but not R5, virus in peripheral blood mononuclear cells (PBMCs). We propose that one functional consequence of secreted Tat is to select against X4 viruses, thereby influencing the early in vivo course of HIV-1 disease.
趋化因子和趋化因子受体在HIV-1感染及嗜性方面发挥着重要作用。CCR5是HIV-1主要的嗜巨噬细胞共受体，而CXC趋化因子受体4（CXCR4）则对嗜T细胞病毒发挥类似作用。一个突出的生物学谜团是，为何在接触R5和X4病毒的新血清转化者中最初仅检测到R5-HIV-1。实际上，X4病毒仅在少数患者中出现，且仅在疾病晚期出现，这表明可能存在针对HIV-1-CXCR4相互作用的早期阴性选择。在此，我们报告称，从病毒感染细胞分泌的HIV-1 Tat蛋白是一种CXCR4特异性拮抗剂。可溶性Tat选择性抑制X4病毒而非R5病毒在外周血单核细胞（PBMC）中的进入和复制。我们提出，分泌型Tat的一个功能后果是对X4病毒进行选择，从而影响HIV-1疾病在体内的早期进程。
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