Reddy T R, Kraus G, Yamada O, Looney D J, Suhasini M, Wong-Staal F
Department of Medicine, University of California at San Diego, La Jolla 92093-0665, USA.
J Virol. 1995 Jun;69(6):3549-53. doi: 10.1128/JVI.69.6.3549-3553.1995.
Virion infectivity factor (vif), a gene found in all lentiviruses, plays an essential role in virus replication in certain target cells. We examined the replication competence of the human immunodeficiency virus type 2 (HIV-2) vif mutant in different T-cell lines and primary cells in comparison with that of the HIV-1 vif mutant. Both mutant viruses were unable to replicate in peripheral blood-derived mononuclear cells but replicated with wild-type efficiency in certain T-cell lines, such as SupT1 and MOLT-4/8. These results confirm the importance of vif in the infection of relevant target cells and imply that some cellular factor(s) could compensate for vif function. However, HIV-1 and HIV-2 vif mutant viruses also show differential replications in other cell lines, suggesting either different threshold requirements for the same cellular factor(s) or the involvement of different factors to compensate for vif-1 and vif-2 functions. By cross complementation experiments, we showed that vif-1 and vif-2 have similar functions. Our studies further indicate the existence of two kinds of nonpermissive cells: H9 is unable to complement HIV-1 delta vif but is susceptible to a one-round infection with HIV-1 delta vif produced from permissive cells. In contrast, U937 is nonpermissive for HIV-2 delta vif produced from permissive cells but, once infected, is able to complement the delta vif function. In both types of nonpermissive cells, a step prior to proviral DNA synthesis is affected.
病毒体感染性因子(vif)是在所有慢病毒中都能找到的一个基因,在某些靶细胞的病毒复制中起着至关重要的作用。我们将2型人类免疫缺陷病毒(HIV-2)vif突变体与HIV-1 vif突变体相比较,检测了其在不同T细胞系和原代细胞中的复制能力。两种突变病毒在外周血来源的单核细胞中均无法复制,但在某些T细胞系,如SupT1和MOLT-4/8中能以野生型效率进行复制。这些结果证实了vif在相关靶细胞感染中的重要性,并暗示某些细胞因子可以补偿vif的功能。然而,HIV-1和HIV-2 vif突变病毒在其他细胞系中也表现出不同的复制情况,这表明对于相同的细胞因子可能存在不同的阈值要求,或者涉及不同的因子来补偿vif-1和vif-2的功能。通过交叉互补实验,我们发现vif-1和vif-2具有相似的功能。我们的研究进一步表明存在两种非允许细胞:H9无法补偿HIV-1 Δvif,但易受来自允许细胞产生的HIV-1 Δvif的单轮感染。相反,U937对来自允许细胞产生的HIV-2 Δvif不允许,但一旦被感染,就能补偿Δvif的功能。在这两种非允许细胞中,前病毒DNA合成之前的一个步骤受到影响。