The impact of human allelic variation on HIV-1 disease

Human allelic variants influence the susceptibility to HIV-1 infection and/or the subsequent rates of disease progression towards AIDS that average ten years, although they vary greatly among infected subjects. In this respect, studies involving multiply exposed persons who remain uninfected, long-term nonprogressors (who remain asymptomatic for fifteen years or more) or, in contrast, rapid progressors (who develop AIDS within two to three years post-infection) as well as seroincident cohorts of patients with defined seroconversion dates have contributed to our comprehension of the effects of different natural human polymorphisms on HIV-1 disease. The current article aims at providing an up-to-date review on these polymorphisms that may be broadly classified into three general categories: (1) those that control viral entry into susceptible cells (namely, chemokine and chemokine receptor polymorphisms), (2) mutational variants of genes involved in immune regulation, such as interleukin-10 (IL-10), interleukin-4 (IL-4), tumor necrosis factor-alpha (TNF-alpha), and mannose-binding lectin (MBL), and (3) polymorphisms in genes involved in the adaptive immune recognition by T cells, [human leukocyte antigen (HLA) type]. Particular emphasis has been placed on the state-of-the-art biotechnological methodologies, such as "spectral genotyping" that utilizes molecular beacons in conjunction with polymerase chain reaction in real-time (real-time-PCR), which were developed to assist with the characterization of some of these determinants. Elucidating the functional role of these factors via the application of such biotechnological assays is expected to further enhance our understanding of the pathogenesis of HIV-1 infection, and, eventually, to enrich our therapeutic arsenal with novel antiviral agents or strategic approaches.