Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response
Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response
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DOI：
10.1172/jci40093
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发表时间：
2009-12-01
影响因子：
15.9
通讯作者：
Mueller-Trutwin, Michaela C.
中科院分区：
文献类型：
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作者：
Jacquelin, Beatrice;Mayau, Veronique;Mueller-Trutwin, Michaela C.
感染AGM型SIV（SIVagm）的非洲绿色猴（AGM）不会发展成慢性免疫激活和AIDS，尽管病毒载量与感染HIV-1的人类和感染RM型SIV（SIVmac）的恒河猴（RM）中检测到的病毒载量相似。由于慢性免疫激活驱动进行性CD 4（+）T细胞耗竭和免疫细胞功能障碍，这些因素是疾病进展的特征，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SIVagm和SIVmac感染后来自AGM和RM的血液和淋巴结来源的CD 4（+）细胞的基因表达谱。急性感染的分子特征的特点是，在这两个物种中，强烈上调I型干扰素刺激的基因（ISGs）。ISG表达恢复到基础水平后，感染后第28天在AGM，但持续在RM，特别是在淋巴结来源的细胞。我们还发现SIVagm。诱导AGM细胞产生IFN-α，并且低IFN-α水平足以诱导强ISG应答。总之，SIV感染在AGM和RM中均引发了体内快速且强烈的IFN-α应答，这种应答仅在AGM中得到有效控制，这可能是主动调节机制的结果。
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.