Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
Semin Nephrol. 2017 Nov;37(6):514-519. doi: 10.1016/j.semnephrol.2017.07.004.
Apolipoprotein L1 (APOL1) genetic variants are potent risk factors for glomerular disease, but one or more additional factors are required for expression of glomerular disease. Uncontrolled or poorly controlled human immunodeficiency virus (HIV) infection is the most potent susceptibility factor for APOL1 nephropathy that has been identified to date. APOL1 variants are associated with HIV-associated nephropathy (HIVAN), a podocyte disease, but not with HIV-immune complex disease, primarily a disease of the mesangium. The mechanism by which HIV brings out the latent glomerular disease risk remains to be defined. There are at least two classes of candidate mechanisms to explain the potent interaction between HIV-1 and APOL1. First, APOL1 variant proteins and HIV accessory proteins implicated in HIVAN may target the same or related intracellular pathways in podocytes. Recent data suggest roles for interleukin 1b and transcription factor EB. Second, features of uncontrolled HIV infection, including increased circulating factors such as interferon, may drive APOL1 gene transcription or act upon podocytes in other ways. Deeper probing of APOL1-HIV interactions may yield insights that will aid in understanding HIVAN, APOL1 nephropathy, and podocyte biology.
载脂蛋白 L1（APOL1）基因突变是肾小球疾病的强烈危险因素，但还需要一个或多个其他因素才能表现出肾小球疾病。目前已确定，未经控制或控制不佳的人类免疫缺陷病毒（HIV）感染是 APOL1 肾病的最强易感性因素。APOL1 变体与 HIV 相关性肾病（HIVAN）有关，这是一种足细胞疾病，但与 HIV 免疫复合物疾病无关，后者主要是系膜疾病。HIV 引发潜在肾小球疾病风险的机制仍有待确定。至少有两类候选机制可以解释 HIV-1 和 APOL1 之间的强烈相互作用。首先，APOL1 变体蛋白和与 HIVAN 相关的 HIV 辅助蛋白可能靶向足细胞中相同或相关的细胞内途径。最近的数据表明白细胞介素 1b 和转录因子 EB 发挥作用。其次，HIV 感染失控的特征，包括循环中干扰素等增加的因子，可能会驱动 APOL1 基因转录，或以其他方式作用于足细胞。更深入地探究 APOL1-HIV 相互作用可能会提供有助于理解 HIVAN、APOL1 肾病和足细胞生物学的见解。
