Li Qingsheng, Estes Jacob D, Duan Lijie, Jessurun Jose, Pambuccian Stefan, Forster Colleen, Wietgrefe Stephen, Zupancic Mary, Schacker Timothy, Reilly Cavan, Carlis John V, Haase Ashley T
Department of Microbiology, University of Minnesota, Minneapolis, MN 55455, USA.
J Infect Dis. 2008 Feb 1;197(3):420-9. doi: 10.1086/525046.
The enteropathic manifestations of the human immunodeficiency virus (HIV) and the simian immunodeficiency virus (SIV) in late infection are usually due to infection by other microbes, but in early infection the viruses themselves cause an enteropathy by heretofore undetermined mechanisms. Here we report that SIV induces massive apoptosis of intestinal epithelial cells lining the small and large bowel, thus identifying apoptosis as the driving force behind the regenerative pathology of early infection. We found that apoptosis of gut epithelium paralleled the previously documented apoptosis and massive depletion of CD4 T cells in gut lamina propria, triggered by established mechanisms of gut epithelial cell apoptosis and, at peak, possibly by virus interactions with GPR15/Bob, an intestinal epithelial cell-associated alternative coreceptor for SIV and HIV-1. Apoptosis in early SIV infection is thus the common theme of the pathological processes that quickly afflict the innate as well as adaptive arms of the gut immune system.
人类免疫缺陷病毒（HIV）和猿猴免疫缺陷病毒（SIV）在晚期感染时的肠道病变表现通常是由其他微生物感染引起的，但在早期感染时，病毒本身通过迄今尚未明确的机制导致肠道病变。在此，我们报告SIV诱导小肠和大肠内衬的肠道上皮细胞大量凋亡，从而确定凋亡是早期感染再生性病理背后的驱动力。我们发现肠道上皮细胞的凋亡与先前记录的肠道固有层中CD4 T细胞的凋亡和大量耗竭平行，这是由肠道上皮细胞凋亡的既定机制引发的，在高峰期可能是由病毒与GPR15/Bob相互作用引发的，GPR15/Bob是一种与肠道上皮细胞相关的SIV和HIV-1替代共受体。因此，早期SIV感染中的凋亡是迅速影响肠道免疫系统固有和适应性分支的病理过程的共同主题。
