Peng Xiaorong, Isnard Stéphane, Lin John, Fombuena Brandon, Bessissow Talat, Chomont Nicolas, Routy Jean-Pierre
Infectious Diseases and Immunity in Global Health Program, Research Institute, McGill University Health Centre, Montréal, QC, Canada.
Chronic Viral Illness Service, McGill University Health Centre, Montréal, QC, Canada.
J Virus Erad. 2021 Feb 15;7(1):100033. doi: 10.1016/j.jve.2021.100033. eCollection 2021 Mar.
The greatest obstacle to an HIV cure is the persistence of latently infected cellular reservoirs in people living with HIV (PLWH) taking antiretroviral therapy (ART). However, no consensus exists on the direct link between local tissue inflammation and the HIV burden. Herein, we have compared the levels of local inflammation, epithelial integrity and HIV DNA between inflamed and non-inflamed colon tissue in a PLWH who underwent a colectomy due to ulcerative colitis. We have observed a 27-fold higher frequency of cells harboring HIV DNA in inflamed compared to non-inflamed colon tissue. Analysis of the expression of occludin-1 and claudin-3 confirmed our macroscopic characterization of inflamed and non-inflamed colon. Our results confirm that increased gut permeability and inflammation are associated with a higher frequency of infected cells and suggest that restoring gut barrier integrity may be used as a strategy to reduce inflammation and HIV persistence in the gut.
对治愈艾滋病病毒(HIV)而言,最大的障碍是接受抗逆转录病毒疗法(ART)的HIV感染者(PLWH)体内持续存在潜伏感染的细胞储存库。然而,对于局部组织炎症与HIV负荷之间的直接联系,目前尚无定论。在此,我们比较了一名因溃疡性结肠炎接受结肠切除术的PLWH患者发炎和未发炎结肠组织中的局部炎症水平、上皮完整性和HIV DNA水平。我们观察到,与未发炎的结肠组织相比,发炎的结肠组织中携带HIV DNA的细胞频率高出27倍。对闭合蛋白-1和紧密连接蛋白-3表达的分析证实了我们对发炎和未发炎结肠的宏观特征描述。我们的结果证实,肠道通透性增加和炎症与更高频率的感染细胞有关,并表明恢复肠道屏障完整性可作为一种策略,用于减少肠道炎症和HIV持续存在。