EFFECTS OF BETA CHEMOKINES ON REPLICATION OF T CELL TROPIC STRAINS OF HIV 1

嗜巨噬细胞(M)的HIV-1准种是优势毒株 在血清转换时和在体内复制 艾滋病毒感染的无症状阶段。在大约40%的 HIV感染者，T细胞(T)嗜性HIV毒株出现为 在艾滋病毒感染过程中的优势物种；这种“转变”到 嗜T菌株优势与CD4+T细胞快速下降有关 和疾病的快速发展。这项研究的目的是 研究β-趋化因子受体CCR5的配体 (MIP-1α、MIP-1β和RANTES)，阻止进入/复制 干扰巨噬细胞(M)亲和性HIV毒株的体外研究 M嗜性HIV利用CCR5作为进入共受体的能力， 影响T嗜性HIV毒株的复制。CD4+的治疗 某些HIV感染者分泌β-趋化因子的T细胞体外培养 被发现促进内源性嗜T细胞的出现或复制 艾滋病毒准种。T嗜血杆菌低接种率的研究 来自未感染的捐赠者的CD4+T细胞中的HIV显著增加 通过用包括MCP-1在内的多种β-趋化因子处理细胞， 它不是CCR5配体。兰特被证明可以增强 T嗜性HIV毒株进入CD4+T细胞，这一效应是 依赖于GI蛋白偶联信号转导；相比之下，其 拮抗剂氨基氧戊烷(AOP)-RANTES抑制M-嗜性进入，但 没有增加T嗜性艾滋病病毒的进入。这些观察结果表明 β-趋化因子可能在以M嗜性为主的转变中发挥作用 T嗜性HIV毒株体内复制和给药 对HIV感染者使用β-趋化因子，以限制 应谨慎对待艾滋病毒的复制和传播，因为 这种治疗可能会导致T嗜性艾滋病毒的加速出现 菌株。

Macrophage (M)-tropic HIV-1 quasispecies are the predominant strains replicating in vivo at the time of seroconversion and during the asymptomatic stages of HIV infection. In approximately 40% of HIV-infected individuals, T cell (T)-tropic HIV strains emerge as the predominant species during the course of HIV infection; this "shift" to T-tropic strain dominance is associated with rapid CD4+ T-cell decline and rapid disease progression. The purpose of this study was to investigate whether the ligands of the beta-chemokine receptor CCR5 (MIP-1alpha, MIP-1beta and RANTES), which block the entry/replication of macrophage (M)-tropic HIV strains in vitro by interfering with the ability of M-tropic HIV to utilize CCR5 as an entry co-receptor, influence the replication of T-tropic HIV strains. Treatment of CD4+ T cells from certain HIV-infected subjects with beta-chemokines in vitro was found to enhance the emergence or replication of endogenous T-tropic HIV quasispecies. The infection efficiency of low inocula of T-tropic HIV in CD4+ T cells from uninfected donors was dramatically increased by treatment of cells with numerous beta-chemokines, including MCP-1, which is not a CCR5 ligand. RANTES was demonstrated to enhance the entry of T-tropic HIV strains into CD4+ T cells and this effect was dependent on Gi protein-coupled signal transduction; in contrast, its antagonist, aminooxypentane (AOP)-RANTES, inhibited M-tropic entry but did not increase T-tropic HIV entry. These observations suggest that beta-chemokines may play a role in the shift from predominantly M-tropic to T-tropic HIV strain replication in vivo and that the administration of beta-chemokines to HIV-infected subjects for the purpose of limiting the replication and spread of HIV should be approached with caution as such treatment may result in the accelerated emergence of T-tropic HIV strains.