Institut Pasteur, Unité de Régulation des Infections Rétrovirales, Paris, France.
J Clin Invest. 2009 Dec;119(12):3544-55. doi: 10.1172/JCI40093.
African green monkeys (AGMs) infected with the AGM type of SIV (SIVagm) do not develop chronic immune activation and AIDS, despite viral loads similar to those detected in humans infected with HIV-1 and rhesus macaques (RMs) infected with the RM type of SIV (SIVmac). Because chronic immune activation drives progressive CD4+ T cell depletion and immune cell dysfunctions, factors that characterize disease progression, we sought to understand the molecular basis of this AGM phenotype. To this end, we longitudinally assessed the gene expression profiles of blood- and lymph node-derived CD4+ cells from AGMs and RMs in response to SIVagm and SIVmac infection, respectively, using a genomic microarray platform. The molecular signature of acute infection was characterized, in both species, by strong upregulation of type I IFN-stimulated genes (ISGs). ISG expression returned to basal levels after postinfection day 28 in AGMs but was sustained in RMs, especially in the lymph node-derived cells. We also found that SIVagm induced IFN-alpha production by AGM cells in vitro and that low IFN-alpha levels were sufficient to induce strong ISG responses. In conclusion, SIV infection triggered a rapid and strong IFN-alpha response in vivo in both AGMs and RMs, with this response being efficiently controlled only in AGMs, possibly as a result of active regulatory mechanisms.
感染非人类灵长类动物绿猴（AGM）的猿猴免疫缺陷病毒（SIVagm）不会发展为慢性免疫激活和艾滋病，尽管其病毒载量与感染 HIV-1 的人类和感染 SIVmac 的恒河猴（RM）相似。由于慢性免疫激活会导致 CD4+T 细胞逐渐耗竭和免疫细胞功能障碍，这些都是疾病进展的特征，我们试图了解这种 AGM 表型的分子基础。为此，我们使用基因组微阵列平台，分别纵向评估了 AGM 和 RM 的血液和淋巴结来源的 CD4+细胞对 SIVagm 和 SIVmac 感染的基因表达谱。在这两个物种中，急性感染的分子特征是强烈上调 I 型干扰素（IFN）刺激基因（ISG）。AGM 中的 ISG 表达在感染后第 28 天恢复到基础水平，但 RM 中的表达持续存在，尤其是在淋巴结来源的细胞中。我们还发现 SIVagm 在体外诱导 AGM 细胞产生 IFN-α，并且低水平的 IFN-α足以诱导强烈的 ISG 反应。总之，SIV 感染在 AGM 和 RM 体内均迅速引发强烈的 IFN-α反应，但只有 AGM 能够有效控制这种反应，这可能是由于积极的调节机制。
