Rappaport J, Arya S K, Richardson M W, Baier-Bitterlich G, Klotman P E
Division of Nephrology, Mount Sinai School of Medicine, New York, NY 10029, USA.
J Mol Med (Berl). 1995 Dec;73(12):583-9. doi: 10.1007/BF00196351.
HIV-1 and HIV-2 are co-endemic in certain geographic areas. HIV-2 is more weakly pathogenic than HIV-1, and progression to AIDS occurs less frequently and over a longer period of time. Recent epidemiologic studies suggest that individuals infected with HIV-2 have a lower risk of HIV-1 infection. Both immune mechanisms and various modes of viral interference have been proposed to account for these results. Our findings, described in this paper, suggest that HIV-2 inhibits HIV-1 replication. To study the molecular interactions between HIV-1 and HIV-2, proviral clones were transfected alone or in combination into the human T cell line CEM. LTR-CAT indicator constructs were included for the purpose of monitoring viral promoter activity. Viral replication in transfected cells was monitored by p24 antigen capture assay of cell culture supernatants and Western blot analysis of cell extracts. HIV-2 inhibited HIV-1 replication as determined by intracellular and extracellular p24 antigen levels. Similar results were obtained with simultaneous virus infection using HIV-1 and HIV-2, rather than transfections of proviral DNA. Using cotransfection of HIV-1 and HIV-2 LTR indicator gene constructs, the mechanism of inhibition was found to be suppression of the HIV-1 LTR by HIV-2. The inhibitory effect of HIV-2 is not due to Tat-2, but appears to discriminate between the HIV-1 and HIV-2 LTRs based on differences in the Tat activation response element, TAR. These results suggest both a molecular mechanism for HIV-2 interference with HIV-1 replication and a potential molecular approach to therapy.
HIV-1和HIV-2在某些地理区域共同流行。HIV-2的致病性比HIV-1弱，进展为艾滋病的情况较少见且发生时间较长。最近的流行病学研究表明，感染HIV-2的个体感染HIV-1的风险较低。免疫机制和各种病毒干扰模式都被提出来解释这些结果。我们在本文中描述的研究结果表明，HIV-2抑制HIV-1复制。为了研究HIV-1和HIV-2之间的分子相互作用，将前病毒克隆单独或组合转染到人T细胞系CEM中。为监测病毒启动子活性而加入了LTR-CAT指示构建体。通过对细胞培养上清液进行p24抗原捕获测定和对细胞提取物进行蛋白质印迹分析来监测转染细胞中的病毒复制。根据细胞内和细胞外p24抗原水平确定，HIV-2抑制HIV-1复制。使用HIV-1和HIV-2同时感染而非转染前病毒DNA也获得了类似结果。通过共转染HIV-1和HIV-2 LTR指示基因构建体，发现抑制机制是HIV-2对HIV-1 LTR的抑制。HIV-2的抑制作用不是由于Tat-2，而是似乎基于Tat激活反应元件TAR的差异区分HIV-1和HIV-2的LTR。这些结果提示了HIV-2干扰HIV-1复制的分子机制以及一种潜在的分子治疗方法。
