Killer immunoglobulin-like receptors and HLA act both independently and synergistically to modify HIV disease progression

• Published in: Genes and immunity Vol. 6; no. 8; pp. 683 - 690
• Main Authors: Gaudieri, S, DeSantis, D, McKinnon, E, Moore, C, Nolan, D, Witt, C S, Mallal, S A, Christiansen, F T
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.12.2005
• Subjects: Acquired immune deficiency syndrome; Acquired Immunodeficiency Syndrome - genetics; Acquired Immunodeficiency Syndrome - immunology; Acquired Immunodeficiency Syndrome - virology; Adult; AIDS; Alleles; Australia - epidemiology; CD4 antigen; CD4 Lymphocyte Count; CD4-Positive T-Lymphocytes; Cell receptors; Cohort Studies; Cross-Sectional Studies; Development and progression; Disease Progression; European Continental Ancestry Group; Female; Genes; Genetic aspects; Genetic diversity; Genetic factors; Genetic Markers; Genotypes; Haplotypes; Health aspects; Histocompatibility antigen HLA; Histocompatibility antigens; HIV; HIV infection; HIV Seropositivity - genetics; HIV Seropositivity - immunology; HIV Seropositivity - virology; HIV-1 - immunology; HIV-1 - physiology; HLA Antigens - genetics; HLA Antigens - immunology; HLA histocompatibility antigens; Human immunodeficiency virus; Human immunodeficiency virus 1; Humans; Immunoglobulin-like receptors; Immunoglobulins; Killer Cells, Natural - immunology; Killer Cells, Natural - virology; KIR protein; Linear Models; Longitudinal Studies; Lymphocytes T; Male; Middle Aged; Multivariate Analysis; Potassium channels (inwardly-rectifying); Receptors, Immunologic - genetics; Survival Analysis; Viral Load; Viremia; Viremia - genetics; Viremia - immunology; Viremia - virology; Australia
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/sj.gene.6364256

Variation in the host response to infection by pathogens including HIV-1 may be conferred by polymorphic genetic factors such as HLA and killer immunoglobulin-like receptors (KIR) genes. Here, we examined KIR and HLA genotype effects on pretreatment viral load, rate of CD4(+) T-cell decline and progression to AIDS among adult HIV-1-infected patients within the Western Australian HIV Study Cohort. In this study, carriage of KIR genes within the 'B' haplotype (eg KIR2DS2) was specifically associated with a more rapid CD4(+) T-cell decline over time and progression to AIDS. In contrast, KIR gene repertoire had no effect on pretreatment viral load while selected HLA alleles (eg HLA-B*5701, HLA-B*2705) demonstrated significant protective effects on viremia. Furthermore, interactions between specific HLA and KIR genes did appear to influence HIV disease progression. The results suggest that host genetic variation within the HLA and KIR gene complexes have clinically relevant effects on the course of HIV-1/AIDS, acting independently as well as synergistically to modify disease progression at multiple levels.