Michaels F H, Hattori N, Gallo R C, Franchini G
Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
AIDS Res Hum Retroviruses. 1993 Oct;9(10):1025-30. doi: 10.1089/aid.1993.9.1025.
The human immunodeficiency virus type 1 (HIV-1) vif gene (viral infectivity gene) plays an important role in viral replication in vitro. We demonstrated that the Vif protein is membrane associated in HIV-1-infected cells and have investigated the role in viral replication of the equivalent gene in HIV-2. We constructed an HIV-2 vif minus mutant and studied its virulence and cellular tropism in vitro. Parallel experiments were also performed with an HIV-1 vif mutant to ascertain whether the two distantly related HIV-2 and HIV-1 genes might exert the same effect on viral replication. The results indicated that both HIV-1 and HIV-2 vif minus cell-free infection was not impaired when the SupT-1 cell line was used. However, differential degrees of impairment in viral replication were observed when other cell lines were used (Molt-3, U-937). Nevertheless, when viral production could not be detected, rescue experiments by coculture with the permissive cell line SupT-1 were generally positive, indicating that the viruses were still present in the inoculated cells. In contrast, when primary human cells (peripheral blood mononuclear cells and purified macrophages) were infected with HIV-1 and HIV-2 vif minus viruses no productive infection was observed and generally no virus was rescued by cocultivation. Thus, like in HIV-1, the vif gene of HIV-2 is crucial for viral infectivity in primary cells and might represent an attractive target for therapy.
人类免疫缺陷病毒1型(HIV-1)的vif基因(病毒感染性基因)在体外病毒复制中起重要作用。我们证明Vif蛋白在HIV-1感染的细胞中与膜相关,并研究了HIV-2中同源基因在病毒复制中的作用。我们构建了一个HIV-2 vif缺失突变体,并在体外研究了其毒力和细胞嗜性。还对HIV-1 vif突变体进行了平行实验,以确定两个亲缘关系较远的HIV-2和HIV-1基因是否可能对病毒复制产生相同的影响。结果表明,当使用SupT-1细胞系时,HIV-1和HIV-2 vif缺失的无细胞感染均未受损。然而,当使用其他细胞系(Molt-3、U-937)时,观察到病毒复制存在不同程度的损害。尽管如此,当检测不到病毒产生时,与允许性细胞系SupT-1共培养的拯救实验通常呈阳性,表明病毒仍存在于接种的细胞中。相比之下,当原代人细胞(外周血单核细胞和纯化的巨噬细胞)感染HIV-1和HIV-2 vif缺失病毒时,未观察到有生产性感染,并且通过共培养通常也无法拯救出病毒。因此,与HIV-1一样,HIV-2的vif基因对原代细胞中的病毒感染性至关重要,可能是一个有吸引力的治疗靶点。