INDUCTION OF HIV 1 REPLICATION IN LATENTLY INFECTED CD4+ T CELLS

某些细胞因子，特别是促炎因子 细胞因子，可增强外周血中正在进行的病毒复制 HIV-1感染者的单个核细胞(PBMC)； 然而，目前尚不清楚这些细胞因子在 潜伏感染静息状态的CD4+T细胞中HIV-1复制的诱导 细胞。我们的研究表明，体外结合 促炎细胞因子白介素6与肿瘤坏死 肿瘤坏死因子-α与免疫调节细胞因子 IL-2是高效的病毒复制诱导剂， 来自HIV感染者的潜伏感染、静息的CD4+T细胞 接受抗逆转录病毒治疗的人和那些天真的 他们正在接受高效抗逆转录病毒治疗(HAART)。 由这种细胞因子组合诱导的病毒复制 在体外，在HAART存在的情况下完全被抑制。vt.给出 包括IL-6、TNF-α和IL-2在内的一系列细胞因子 在淋巴组织的微环境中大量表达 含有潜伏的病毒库的组织，通过 这种细胞因子的结合可能在一定程度上解释了 观察到可检测到的血浆病毒血症在 停止HAART的艾滋病毒感染者。 此外，由于这些受感染的细胞很可能死于 病毒激活和HAART防止病毒传播到 相邻细胞，观察到这种细胞因子的组合 可以显著地诱导病毒在这个蓄水池中复制 激活介导的细胞数量减少的重要意义 接受HAART的患者中HIV的潜伏储备库。

Certain cytokines, particularly pro-inflammatory cytokines, can enhance ongoing viral replication in peripheral blood mononuclear cells (PBMCs) of HIV-1 infected individuals; however, it is unclear what role these cytokines play in the induction of HIV-1 replication in latently infected, resting CD4+ T cells. Our study demonstrates that the in vitro combination of the pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha together with the immunoregulatory cytokine IL-2 are potent inducers of viral replication in highly purified, latently infected, resting CD4+ T cells derived from HIV-infected individuals who are antiretroviral therapy naive as well as those who are receiving highly active antiretroviral therapy (HAART). Viral replication induced by this combination of cytokines was completely suppressed in the presence of HAART in vitro. Given that an array of cytokines, including IL-6, TNF-alpha and IL-2 are copiously expressed in the microenvironment of the lymphoid tissues, which harbor the latent viral reservoirs, induction of HIV by this combination of cytokines may in part explain the commonly observed reappearance of detectable plasma viremia in HIV-infected individuals in whom HAART was discontinued. Moreover, since it is likely that these infected cells die upon activation of virus and that HAART prevents spread of virus to adjacent cells, the observation that this combination of cytokines can markedly induce viral replication in this reservoir may have important implications for the activation- mediated diminution of the latent reservoir of HIV in patients receiving HAART.