Mehandru Saurabh, Dandekar Satya
Division of Gastroenterology, Mount Sinai School of Medicine, New York, New York, USA.
Curr Opin HIV AIDS. 2008 Jan;3(1):22-7. doi: 10.1097/COH.0b013e3282f331b0.
Here we present recent studies examining the gastrointestinal tract during primary HIV and simian immunodeficiency virus infections and emphasizing the onset of severe pathologic processes that are not adequately reflected in peripheral blood. We discuss these findings and hypotheses relating to the role of the gastrointestinal tract in HIV-1 pathogenesis.
High levels of viral replication in the gastrointestinal mucosa during primary HIV and simian immunodeficiency virus infections lead to severe depletion of effector memory CD4 T cells coinciding with increased immune activation and mucosal damage. Viral reservoirs established at this stage appear to be persistent over the course of infection and during therapy. In the simian immunodeficiency virus model of AIDS, onset of the impaired intestinal epithelial barrier function and renewal was observed during primary viral infection. Dysfunction of the mucosal immune system and the epithelial barrier may contribute to viral persistence and impaired responses to microbial pathogens in infected individuals.
A better understanding of the impact of HIV infection on the mucosal immune system may help in the development of newer preventive and therapeutic strategies directed against the virus.
在此我们展示近期的研究,这些研究对原发性人类免疫缺陷病毒(HIV)和猿猴免疫缺陷病毒感染期间的胃肠道进行了检查,并着重关注了严重病理过程的起始情况,而这些情况在外周血中并未得到充分体现。我们讨论了这些发现以及与胃肠道在HIV-1发病机制中作用相关的假说。
在原发性HIV和猿猴免疫缺陷病毒感染期间,胃肠道黏膜中高水平的病毒复制导致效应记忆CD4 T细胞严重耗竭,同时免疫激活增加和黏膜损伤。在此阶段建立的病毒储存库在感染过程和治疗期间似乎持续存在。在艾滋病的猿猴免疫缺陷病毒模型中,在原发性病毒感染期间观察到肠道上皮屏障功能和更新受损。黏膜免疫系统和上皮屏障的功能障碍可能导致病毒持续存在,并损害感染个体对微生物病原体的反应。
更好地理解HIV感染对黏膜免疫系统的影响可能有助于开发针对该病毒的更新的预防和治疗策略。