MOLECULAR ANALYSIS OF THIRD VARIABLE ENVELOPE REGION OF SIV: AIDS

与人类免疫缺陷病毒1型(HIV-1)V3相比， 猴免疫缺陷病毒(SIV)V3似乎不可变 在持续感染的猕猴外周血白细胞中 在实验室分离的菌株中也是如此。然而，相当大的基因 艾滋病致死恒河猴组织中V3基因的变异 用克隆的SIVmac239感染后观察到。这个 SIV V3的氨基酸变异模式不是随机的(类似于 那些在HIV-1 V3中的人)。组成预测冠状结构的氨基酸 和V3环的茎区保存得很好；然而， 树冠两侧的区域变化很大。 含有一株自然突变的V3的SIV的分子克隆 Gp120中的序列显示出较高的复制和细胞病变能力 比SIVmac239对T淋巴细胞的影响更大。突变的V3基因更加积极 比SIVmac239的V3更带电和亲水性，这些都是性质 与HIV-1的V3类似，具有高复制和细胞病变能力 T淋巴细胞。这些观察结果强烈表明，SIV V3 可能会受到与HIV-1类似的选择压力 V3，提示SIV中的V3在SIV的发病机制中起一定作用。 SIV感染，就像它在HIV-1中所做的那样。 确定SIV V3对病毒细胞的生物学意义 嗜T细胞和巨噬细胞嗜性克隆SIV的V3 与自然突变的V3序列交换，以及V3重组 产生了病毒。重组EV/T3-MTV3在人T细胞系中的表达 病毒复制与SIVmac239一样好，而不是 EV/T3在人T细胞系中复制。同样，239-MTV3 显示出人类T细胞复制能力显著降低 与SIVmac239进行比较。在恒河猴淋巴细胞培养中， EV/T3-MTV3的复制能力显著低于 EV/T3,239-MTV3重组体的复制效果好于SIVmac239。 这些数据表明，EV/T3和SIVmac239的V3序列 确定这些病毒在人T细胞中的复制潜能 细胞系和恒河猴淋巴细胞体外培养。

In contrast to human immunodeficiency virus type 1 (HIV-1) V3, the simian immunodeficiency virus (SIV) V3 does not appear to be variable in peripheral blood leukocytes of persistently infected macaques as well as among laboratory isolates. However, considerable genetic variation in V3 in tissues of rhesus macaques that died from AIDS following infection with cloned SIVmac239 has been observed. The pattern of amino acid variation in SIV V3 was not random (similar to those in HIV-1 V3). The amino acids comprising the predicted crown and stem regions of the V3 loop were well conserved; however, the regions flanking the crown on both sides were highly variable. Molecularly cloned SIV containing one of the naturally mutated V3 sequences in gp120 showed higher replicative and cytopathic ability for T-lymphocytes than SIVmac239. The mutated V3 is more positively charged and hydrophilic than V3 of SIVmac239, which are properties similar to V3 of HIV-1 with high replicative and cytopathic ability for T-lymphocytes. These observations strongly suggest that SIV V3 might be subjected to similar selective pressures that occur on HIV-1 V3, and indicate that V3 in SIV plays a role in the pathogenesis of SIV infections, as it does in HIV-1. To determine the biological significance of SIV V3 for viral cell tropism the V3 of T cell-tropic and macrophage-tropic cloned SIV was exchanged with the naturally mutated V3 sequences, and V3 recombinant viruses were generated. In human T cell lines, Ev/T3-mtv3 recombinant virus replicated as well as SIVmac239, in contrast to the inability of Ev/T3 to replicate in human T cell lines. Similarly, 239-mtv3 displayed dramatically reduced replicative potential in human T cell lines compared to SIVmac239. In rhesus macaque lymphocyte cultures, Ev/T3-mtv3 showed remarkably reduced replicative potential compared to Ev/T3, and the 239-mtv3 recombinant replicated better than SIVmac239. These data demonstrate that the V3 sequences of Ev/T3 and SIVmac239 determine the replicative potential of these viruses in human T cell lines and rhesus lymphocytes in vitro.