HIV-1 TROPISM FOR MONONUCLEAR PHAGOCYTES CAN BE DETERMINED BY REGIONS OF GP120 OUTSIDE THE CD4-BINDING DOMAIN
HIV-1 TROPISM FOR MONONUCLEAR PHAGOCYTES CAN BE DETERMINED BY REGIONS OF GP120 OUTSIDE THE CD4-BINDING DOMAIN
复制标题
DOI：
10.1038/348069a0
复制
发表时间：
1990-11-01
期刊：
影响因子：
64.8
通讯作者：
CHEN, ISY
中科院分区：
文献类型：
--
作者：
OBRIEN, WA;KOYANAGI, Y;CHEN, ISY
单核吞噬细胞系统的细胞是大多数组织中产生 HIV-1 的主要细胞，包括中枢神经系统 (CNS)1-4、脊髓5、肺6和皮肤7,8；感染分别与痴呆 9,10、神经病 11-13、肺炎 9,14 和皮炎 15,16 相关。不同的 HIV-1 分离株有效感染单核吞噬细胞的能力存在显着差异 17,18。在这里，我们描述了中枢神经系统衍生的分离物 HIV-1JR-FL 的分子克隆，它可以在单核吞噬细胞中有效复制。对感染后早期事件的聚合酶链反应分析表明，逆转录之前病毒复制的早期阶段决定了向性。通过构建重组病毒对嗜巨噬细胞表型进行遗传图谱分析表明，单核吞噬细胞的感染性可以通过 HIV-1JR-FL 的 gp120 糖蛋白的 157 个氨基酸区域来确定。值得注意的是，该区域位于先前定义的 CD4 结合域的上游19。我们提出，单核吞噬细胞向性的至少一个决定因素涉及靶细胞与不同于 CD4 结合域的 gp120 区域的相互作用。
CELLS of the mononuclear phagocyte system are the predominant cell producing HIV-1 in most tissues, including the central nervous system (CNS)1–4, spinal cord5, lung6and skin7,8; infection is associated with dementia9,10, neuropathy11–13, pneumonitis9,14and dermatitis15,16respectively. Different HIV-1 isolates vary markedly in their ability to infect mononuclear phagocytes productively17,18. Here we describe molecular clones of a CNS-derived isolate, HIV-1JR–FLwhich can replicate efficiently in mononuclear phagocytes. Analysis by polymerase chain reaction of early events after infection indicates that the early phase of viral replication before reverse transcription determines tropism. Genetic mapping of the macrophage-tropic phenotype by construction of recombinant viruses indicates that mononuclear phagocyte infectivity can be determined by a 157-amino-acid region of the gp120 glycoprotein of HIV-1JR–FL. Significantly, this region is upstream from the previously defined CD4-binding domain19. We propose that at least one determinant for mononuclear phagocyte tropism involves target cell interactions with regions of gp120 distinct from the CD4-binding domain.