title: Heterozygosity for a defective gene for CC chemokine receptor 5 is not the sole determinant for the immunologic and virologic phenotype of HIV-infected long-term nonprogressors.
abstract: HIV-1-infected long-term nonprogressors are a heterogeneous group of individuals with regard to immunologic and virologic markers of HIV-1 disease. CC chemokine receptor 5 (CCR5) has recently been identified as an important coreceptor for HIV-1 entry into CD4+ T cells. A mutant allele of CCR5 confers a high degree of resistance to HIV-1 infection in homozygous individuals and partial protection against HIV disease progression in heterozygotes. The frequency of CCR5 heterozygotes is increased among HIV-1- infected long-term nonprogressors compared with progressors; however, the host defense mechanisms responsible for nonprogression in CCR5 heterozygotes are unknown. We hypothesized that nonprogressors who were heterozygous for the mutant CCR5 gene might define a subgroup of nonprogressors with higher CD4+ T cell counts and lower viral load compared with CCR5 wild-type nonprogressors. However, in a cohort of 33 HIV-1-infected long-term nonprogressors, those who were heterozygous for the mutant CCR5 gene were indistinguishable from CCR5 wild-type nonprogressors with regard to all measured immunologic and virologic parameters. Although epidemiologic data support a role for the mutant CCR5 allele in the determination of the state of long-term nonprogression in some HIV-1- infected individuals, it is not the only determinant. Furthermore, long-term nonprogressors with the wild-type CCR5 genotype are indistinguishable from heterozygotes from an immunologic and virologic standpoint.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
authors.forename: O J
authors.initials: OJ
authors.lastname: Cohen
authors.forename: M
authors.initials: M
authors.lastname: Vaccarezza
authors.forename: G K
authors.initials: GK
authors.lastname: Lam
authors.forename: B F
authors.initials: BF
authors.lastname: Baird
authors.forename: K
authors.initials: K
authors.lastname: Wildt
authors.forename: P M
authors.initials: PM
authors.lastname: Murphy
authors.forename: P A
authors.initials: PA
authors.lastname: Zimmerman
authors.forename: T B
authors.initials: TB
authors.lastname: Nutman
authors.forename: C H
authors.initials: CH
authors.lastname: Fox
authors.forename: S
authors.initials: S
authors.lastname: Hoover
authors.forename: J
authors.initials: J
authors.lastname: Adelsberger
authors.forename: M
authors.initials: M
authors.lastname: Baseler
authors.forename: J
authors.initials: J
authors.lastname: Arthos
authors.forename: R T
authors.initials: RT
authors.lastname: Davey
authors.forename: R L
authors.initials: RL
authors.lastname: Dewar
authors.forename: J
authors.initials: J
authors.lastname: Metcalf
authors.forename: D J
authors.initials: DJ
authors.lastname: Schwartzentruber
authors.forename: J M
authors.initials: JM
authors.lastname: Orenstein
authors.forename: S
authors.initials: S
authors.lastname: Buchbinder
authors.forename: A J
authors.initials: AJ
authors.lastname: Saah
authors.forename: R
authors.initials: R
authors.lastname: Detels
authors.forename: J
authors.initials: J
authors.lastname: Phair
authors.forename: C
authors.initials: C
authors.lastname: Rinaldo
authors.forename: J B
authors.initials: JB
authors.lastname: Margolick
authors.forename: G
authors.initials: G
authors.lastname: Pantaleo
authors.forename: A S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D054407:Chemokine CCL4; D018946:Chemokine CCL5 / Q000097:blood; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification / Q000472:pathogenicity*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008198:Lymph Nodes / Q000737:chemistry / Q000821:virology; D019402:Macrophage Inflammatory Proteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D009154:Mutation; D019713:Receptors, CCR5 / Q000235:genetics* / Q000378:metabolism; D017464:Receptors, Complement 3d / Q000032:analysis; D019562:Viral Load
chemical_list: D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019402:Macrophage Inflammatory Proteins; D019713:Receptors, CCR5; D017464:Receptors, Complement 3d