Genetic Susceptibility, HIV Infection, and the Kidney

Abstract

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.

APOL1 Variants Increase Risk for FSGS and HIVAN but Not IgA Nephropathy

“…[1][2][3][4] Family members of African Americans with ESRD also have a higher incidence of kidney failure, suggesting that genetic susceptibility in part accounts for this skewed epidemiology. 5,6 In 2008, two independent studies demonstrated that variants on chromosome 22q13 were highly associated with the risk of FSGS, HIVAN, and nondiabetic ESRD among African Americans and explained much of the increased risk of kidney failure in this population (per alleles odds ratios [ORs] of 3 to 4).…”

Individual Genetic Variations Directly Effect Polarization of Cytokine Responses to Superantigens Associated with Streptococcal Sepsis: Implications for Customized Patient Care

“…H ost genetic variations can profoundly affect susceptibility to infectious diseases and can modulate disease manifestations and outcomes (1)(2)(3)(4)(5)(6)(7)(8)(9). This fact is particularly true of infections with group A streptococci (GAS), which are important human pathogens that rank among the top 10 killer pathogens (10).…”

“…In addition to inherent and environmental factors, host genetic variations play an important role in susceptibility and outcomes of virtually all infectious diseases (1,(6)(7)(8)(9)(31)(32)(33)(34)(35)(36)(37)(38). We were specifically interested in determining the role of HLA-II allelic variations in GAS sepsis, because these highly polymorphic HLA-II molecules play a pivotal role in SAg presentation to T cells.…”

DC-specific ICAM-3-grabbing nonintegrin mediates internalization of HIV-1 into human podocytes

“…Podocyte dysfunction appears to be the result of the combination of the direct effect of viral gene product expression (66,68), the specific host, and genetic factors (26,28,30,44). However, much of our understanding of the effect of HIV-1 on podocytes is related to the rodent models, which allow only the study of the postentry phase of the HIV-1 life cycle; therefore, little is known about the interaction between HIV-1 and human podocytes in general, and the mechanism involved in podocyte HIV-1 entry in particular.…”