EFFECTS OF COCAINE ON HPA AXIS IN MACAQUE MOTHER & FETUS

虽然已知HIV-1V3在确定病毒细胞方面很重要 嗜性和辅助受体的使用，对SIV的作用知之甚少 V3.这项研究的目的是调查研究的意义 SIV V3用于病毒细胞亲和性和辅助受体用途。在这项研究中，我们 使用了三种具有不同细胞取向的分子克隆SIV， 共受体用法和V3序列T细胞嗜性SIVmacEvT3使用 CXCR4作为共受体，使用CCR5的人T细胞系嗜性SIVmac239， 和使用CCR5的嗜巨噬细胞SIVmacEvM3。我们已经交换了V3 每个克隆的SIV序列与其他克隆的序列一起构建 V3重组病毒。我们从V3重组体获得的数据 结果表明，每个SIV的细胞趋向性和辅助受体用途是 主要由V3序列决定。定点突变 研究进一步证明，氨基酸的电荷 在SIV中，V3序列在决定 病毒细胞的嗜性和受体的使用。这表明， 像HIV-1一样，SIV的V3序列的电荷有助于 Gp120中共受体结合位点的形成，可能包含 V3区域或受其构象影响。有趣的是， 一些构建的突变病毒可以同时使用CXCR4和CCR5 对于病毒进入，类似于双嗜性HIV-1。由于EvT3使用 CXCR4，而不是使用CCR5的239，可诱导快速而严重的CD4+T细胞 在猕猴的消耗中，重要的是要检查 双嗜性SIV在体内的致病潜能。进一步研究与 使用辅受体特异性SIV克隆的恒河猴模型 利用CXCR4、CCR5或CXCR4和CCR5将提供重要的 信息，以更好地了解 艾滋病患者HIV-1辅受体由CCR5变为CXCR4资金来源 NIH RR00163(项目2)出版：Martin K，Hgen S，KoDama T. SIV CXCR4使用的遗传决定因素V1和V3的作用 序列。在第16届非人灵长类动物模型年度研讨会上 艾滋病(1998年10月7日至10日在佐治亚州亚特兰大举行)(摘要3)。

While HIV-1 V3 is known to be important in determining viral cell tropism and coreceptor usage, little is known about the role of SIV V3. The objective of this study is to investigate the significance of SIV V3 for viral cell tropism and coreceptor usage. In this study, we have used three molecularly cloned SIV with distinct cell tropisms, coreceptor usages and the V3 sequences T cell-tropic SIVmacEvT3 using CXCR4 as a coreceptor, human T cell line-tropic SIVmac239 using CCR5, and macrophage-tropic SIVmacEvM3 using CCR5. We have exchanged V3 sequences of each cloned SIV with those of other clones to construct V3 recombinant viruses. Our data obtained from V3 recombinants have shown that the cell tropism and coreceptor usage of each SIV are primarily determined by the V3 sequences. Site-specific mutagenesis studies have further demonstrated that the charge of the amino acids within SIV V3 sequences plays an important role in determining the viral cell tropisms an d corecep tor usage. This suggests that the charge of V3 sequences of SIV, like those of HIV-1, contributes to the formation of coreceptor binding sites in gp120, which may contain the V3 region or be conformationally influenced by it. Interestingly, some of the constructed mutant viruses could use both CXCR4 and CCR5 for virus entry, similar to dual-tropic HIV-1. Since EvT3 using CXCR4, but not 239 using CCR5, induces rapid and severe CD4+ T cell depletion in rhesus macaques, it will be important to examine the pathogenic potential of dual-tropic SIV in vivo. Further studies with the rhesus macaque model using coreceptor-specific SIV clones that utilize CXCR4, CCR5 or CXCR4 and CCR5 will provide important information to better understand the mechanisms and significance of HIV-1 coreceptor changes from CCR5 to CXCR4 in AIDS patients. FUNDING NIH RR00163 (Project 2) PUBLICATIONS Martin K, Hagen S, Kodama T. Genetic determinants of SIV CXCR4 usage the role of V1 and V3 sequences. In 16th Annual Symposium on Nonhuman Primate Models for AIDS (held in Atlanta, GA, October 7-10, 1998) (abstract 3).