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

某些细胞因子，特别是促炎细胞因子 细胞因子，可以增强外周血中正在进行的病毒复制 HIV-1感染个体的单核细胞（PBMC）; 然而，目前还不清楚这些细胞因子在肿瘤发生中的作用。 HIV-1在潜伏感染、静止CD 4 + T细胞中复制诱导 细胞我们的研究表明，在体外的组合， 促炎细胞因子白细胞介素-6与肿瘤坏死 因子（TNF）-α与免疫调节细胞因子 IL-2是高度纯化的， 来自HIV感染者的潜伏感染的静息CD 4 + T细胞 未接受过抗逆转录病毒治疗的个体以及 正在接受高效抗逆转录病毒治疗（HAART）的患者。 由这种细胞因子组合诱导的病毒复制是 在体外HAART存在下完全抑制。给定 一系列细胞因子，包括IL-6，TNF-α和IL-2， 在淋巴微环境中大量表达， 组织，其中窝藏潜伏的病毒水库，诱导艾滋病毒， 这种细胞因子的组合可能部分解释了 观察到可检测的血浆病毒血症的重现， 停止HAART治疗的HIV感染者。 此外，由于这些受感染的细胞很可能在 HAART可以防止病毒的传播， 观察到这种细胞因子的组合 可以显著诱导病毒在这个储库中复制， 对活化介导的 接受高效抗逆转录病毒治疗的患者体内潜伏的艾滋病病毒库。

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.