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Genetic Susceptibility, HIV Infection, and the Kidney

Department of Medicine, Division of Nephrology, College of Physicians and Surgeons, Columbia University, New York, New York

Address correspondence to: Dr. Ali G. Gharavi, Department of Medicine, Columbia University College of Physicians and Surgeons, 630 W 168th street, P&S 10-432 New York, NY 10032. Phone: 212-342-1277; Fax: 212-305-3475; E-mail: ag2239{at}columbia.edu

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.