Kiryluk Krzysztof, Martino Jeremiah, Gharavi Ali G
Department of Medicine, Division of Nephrology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Clin J Am Soc Nephrol. 2007 Jul;2 Suppl 1:S25-35. doi: 10.2215/CJN.00320107.
In recent years, the sequencing of mammalian and microbial genomes has provided the opportunity to study how genetic variation in the host and pathogen influence the course of infectious disease. In the case of HIV-1 infection, such studies have led to identification of key viral proteins that determine pathogenicity, immune evasion, or drug resistance. In addition, candidate gene association studies have uncovered a large number of host genetic variants that influence the outcome of infection and some organ-specific complications. HIV-associated nephropathy (HIVAN) is a pathologically distinct complication of HIV infection. Interindividual variability in incidence, skewed ethnic distribution, and familial aggregation of HIVAN with other forms of ESRD have suggested genetic susceptibility as a major contributing factor. This article reviews the host genetic factors that influence the course of HIV-1 infection and discusses murine models that have increased the understanding of HIVAN pathogenesis and demonstrated the role of genetic background on determination of disease.
近年来，哺乳动物和微生物基因组测序为研究宿主和病原体的基因变异如何影响传染病进程提供了契机。就人类免疫缺陷病毒1型（HIV-1）感染而言，此类研究已促成了对决定致病性、免疫逃逸或耐药性的关键病毒蛋白的识别。此外，候选基因关联研究还发现了大量影响感染结局及某些器官特异性并发症的宿主基因变异。HIV相关性肾病（HIVAN）是HIV感染在病理上有别于其他病症的一种并发症。HIVAN在发病率上的个体差异、种族分布不均以及与其他形式终末期肾病的家族聚集现象均表明，遗传易感性是一个主要促成因素。本文综述了影响HIV-1感染进程的宿主遗传因素，并讨论了有助于加深对HIVAN发病机制的理解以及证明遗传背景在疾病决定中作用的小鼠模型。
