Veazey Ronald, Lackner Andrew
Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, LA 70433, USA.
AIDS Rev. 2003 Oct-Dec;5(4):245-52.
Recent progress in HIV-1 and SIV pathogenesis has revealed that mucosal tissues, primarily the gastrointestinal tract, are major sites for early viral replication and CD4+ T-cell destruction, and may be the major viral reservoir, even in patients receiving HAART. This is likely attributable to the fact that the majority of mucosal CD4+ T-cells co-expressing chemokine receptors requited for HIV-1 entry, reside in mucosal tissues. Furthermore, the intestinal mucosal immune system is continuously bombarded by dietary antigens, resulting in continual lymphocyte activation, dissemination, and homing of these activated lymphocytes (including CCR5+CD4+ T-cells) throughout mucosal tissues. Thus, the intestinal immune system represents a very large target for HIV-infection, which is continually generating newly activated CD4+ T-cells that are the preferred target of infection. Thus, HIV-1 appears uniquely adapted to persist and thrive in the mucosal-tissue environment. The selective loss of intestinal CD4+ T-cells from immune-effector sites is also likely to explain, at least in part, the preponderance of opportunistic infections at mucosal sites. It is increasingly evident that effective therapies and vaccines must be directed towards eliminating HIV-1 in mucosal tissue reservoirs, protecting mucosal CD4+ T-cells and stimulating effective mucosal immune responses.
人类免疫缺陷病毒1型（HIV-1）和猴免疫缺陷病毒（SIV）发病机制的最新进展表明，黏膜组织，主要是胃肠道，是病毒早期复制和CD4+T细胞破坏的主要部位，甚至在接受高效抗逆转录病毒治疗（HAART）的患者中，黏膜组织也可能是主要的病毒储存库。这可能归因于大多数共表达HIV-1进入所需趋化因子受体的黏膜CD4+T细胞存在于黏膜组织中。此外，肠道黏膜免疫系统不断受到饮食抗原的攻击，导致淋巴细胞持续激活、扩散，以及这些激活的淋巴细胞（包括CCR5+CD4+T细胞）在整个黏膜组织中的归巢。因此，肠道免疫系统是HIV感染的一个非常大的靶标，它不断产生新激活的CD4+T细胞，而这些细胞是感染的首选靶标。因此，HIV-1似乎特别适应在黏膜组织环境中持续存在并大量繁殖。肠道CD4+T细胞从免疫效应部位的选择性丢失也可能至少部分解释了黏膜部位机会性感染的优势。越来越明显的是，有效的治疗方法和疫苗必须针对消除黏膜组织储存库中的HIV-1、保护黏膜CD4+T细胞以及刺激有效的黏膜免疫反应。
