title: CCL3L1 and CCR5 influence cell-mediated immunity and affect HIV-AIDS pathogenesis via viral entry-independent mechanisms.
abstract: Although host defense against human immunodeficiency virus 1 (HIV-1) relies mainly on cell-mediated immunity (CMI), the determinants of CMI in humans are poorly understood. Here we demonstrate that variations in the genes encoding the chemokine CCL3L1 and HIV coreceptor CCR5 influence CMI in both healthy and HIV-infected individuals. CCL3L1-CCR5 genotypes associated with altered CMI in healthy subjects were similar to those that influence the risk of HIV transmission, viral burden and disease progression. However, CCL3L1-CCR5 genotypes also modify HIV clinical course independently of their effects on viral load and CMI. These results identify CCL3L1 and CCR5 as major determinants of CMI and demonstrate that these host factors influence HIV pathogenesis through their effects on both CMI and other viral entry-independent mechanisms.
authors.affiliation: Infectious Disease Clinical Research Program, Wilford Hall United States Air Force Medical Center, Lackland Air Force Base, Texas 78236, USA. mdolan@hjf.org
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Dolan
authors.forename: Hemant
authors.initials: H
authors.lastname: Kulkarni
authors.forename: Jose F
authors.initials: JF
authors.lastname: Camargo
authors.forename: Weijing
authors.initials: W
authors.lastname: He
authors.forename: Alison
authors.initials: A
authors.lastname: Smith
authors.forename: Juan-Manuel
authors.initials: JM
authors.lastname: Anaya
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miura
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Hecht
authors.forename: Manju
authors.initials: M
authors.lastname: Mamtani
authors.forename: Florencia
authors.initials: F
authors.lastname: Pereyra
authors.forename: Vincent
authors.initials: V
authors.lastname: Marconi
authors.forename: Andrea
authors.initials: A
authors.lastname: Mangano
authors.forename: Luisa
authors.initials: L
authors.lastname: Sen
authors.forename: Rosa
authors.initials: R
authors.lastname: Bologna
authors.forename: Robert A
authors.initials: RA
authors.lastname: Clark
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Anderson
authors.forename: Judith
authors.initials: J
authors.lastname: Delmar
authors.forename: Robert J
authors.initials: RJ
authors.lastname: O'Connell
authors.forename: Andrew
authors.initials: A
authors.lastname: Lloyd
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Martin
authors.forename: Seema S
authors.initials: SS
authors.lastname: Ahuja
authors.forename: Brian K
authors.initials: BK
authors.lastname: Agan
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Steven G
authors.initials: SG
authors.lastname: Deeks
authors.forename: Sunil K
authors.initials: SK
authors.lastname: Ahuja
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000503:physiopathology; D019742:Chemokines, CC / Q000378:metabolism / Q000502:physiology*; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007111:Immunity, Cellular; D019713:Receptors, CCR5 / Q000502:physiology*; D019562:Viral Load
chemical_list: C492767:CCL3L1 protein, human; D019742:Chemokines, CC; D019713:Receptors, CCR5