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Human Genetic DiversityFunctional Consequences for Health and Disease$
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Julian C. Knight

Print publication date: 2009

Print ISBN-13: 9780199227693

Published to Oxford Scholarship Online: September 2009

DOI: 10.1093/acprof:oso/9780199227693.001.0001

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Human genetic diversity and HIV

Human genetic diversity and HIV

(p.365) Chapter 14 Human genetic diversity and HIV
Human Genetic Diversity

Julian C. Knight

Oxford University Press

Human genetic variation modulates susceptibility to infection with the human immunodeficiency virus (HIV) and progression to acquired immunodeficiency syndrome (AIDS) through diverse mechanisms including viral entry to cells, barriers to infection within cells, cytokines, cell mediated and innate immunity. Diversity in the chemokine coreceptor genes and their natural ligands are discussed including CCR5, CCR2, CXCR2, CCL5, and SDF-1. The impact of copy number variation in the chemokine gene CCL3L1, a natural ligand of CCR5, in susceptibility to HIV-1 and the rate of disease progression is described. The role of TRIM5 in blocking HIV-1 replication soon after viral entry into cells is also described together with the impact of retroviruses during primate evolution. The role of variation in human leucocyte antigens (HLA) and killer immunoglobulin-like receptors (KIRs) is reviewed including evidence for heterozygote advantage and the role of HLA in determining viral set point prior to onset of AIDS.

Keywords:   human immunodeficiency virus, HIV, retrovirus, acquired immunodeficiency syndrome, AIDS, genetic variation, CCR5, CCL3L1, copy number variation, heterozygote advantage

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