title: CCR5 expression, haplotype and immune activation in protection from infection in HIV-exposed uninfected individuals in HIV-serodiscordant relationships.
abstract: Several host factors have been implicated in resistance to HIV infection in individuals who remain HIV-seronegative despite exposure. In a cohort of HIV-serodiscordant heterosexual couples, we investigated interactions between systemic inflammation and T-cell activation in resistance to HIV infection. Males and females in stable long-term relationships with either HIV-infected or uninfected partners were recruited, blood T-cell activation (CD38, HLA-DR, CCR5 and Ki67) and plasma cytokine concentrations were evaluated. The HIV-negative exposed individuals had significantly lower frequencies of CCR5+CD4+and CD8+T cells than unexposed individuals. Mean fluorescence intensity of CCR5 expression on CD4+T cells was significantly lower in HIV-negative exposed than unexposed individuals. Protective CCR5 haplotypes (HHA/HHF*2, HHF*2/HHF*2, HHC/HHF*2, HHA/HHA, HHA/HHC and HHA/HHD) tended to be over-represented in exposed compared with unexposed individuals (38% versus 28%, P = 0·58) whereas deleterious genotypes (HHC/HHD, HHC/HHE, HHD/HHE, HHD/HHD and HHE/HHE) were under-represented (26% versus 44%; P = 0·16). Plasma concentrations of interleukin-2 (P = 0·02), interferon-γ (P = 0·05) and granulocyte-macrophage colony-stimulating factor (P = 0·006) were lower in exposed compared with unexposed individuals. Activation marker expression and systemic cytokine concentrations were not influenced by gender. We conclude that the dominant signature of resistance to HIV infection in this cohort of exposed but uninfected individuals was lower T-cell CCR5 expression and plasma cytokine concentrations.
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.|NRF-DST Centre of Excellence in HIV Prevention, CAPRISA, Durban, South Africa.
authors.forename: Shameem Z
authors.initials: SZ
authors.lastname: Jaumdally
authors.affiliation: Centre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa.|Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Anabela
authors.initials: A
authors.lastname: Picton
authors.affiliation: Centre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa.|Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Caroline T
authors.initials: CT
authors.lastname: Tiemessen
authors.affiliation: Centre for HIV and STIs, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa.|Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Maria
authors.initials: M
authors.lastname: Paximadis
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Heather B
authors.initials: HB
authors.lastname: Jaspan
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Hoyam
authors.initials: H
authors.lastname: Gamieldien
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.|NRF-DST Centre of Excellence in HIV Prevention, CAPRISA, Durban, South Africa.
authors.forename: Lindi
authors.initials: L
authors.lastname: Masson
authors.affiliation: Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa.
authors.forename: David
authors.initials: D
authors.lastname: Coetzee
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.|National Health Laboratory Service, Cape Town, South Africa.
authors.forename: Anna-Lise
authors.initials: AL
authors.lastname: Williamson
authors.affiliation: Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa.
authors.forename: Francesca
authors.initials: F
authors.lastname: Little
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.|NRF-DST Centre of Excellence in HIV Prevention, CAPRISA, Durban, South Africa.
authors.forename: Pamela P
authors.initials: PP
authors.lastname: Gumbi
authors.affiliation: Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.|NRF-DST Centre of Excellence in HIV Prevention, CAPRISA, Durban, South Africa.|National Health Laboratory Service, Cape Town, South Africa.
authors.forename: Jo-Ann S
authors.identifier: 0000-0002-1471-4245
authors.initials: JS
authors.lastname: Passmore
mesh_terms: D000328:Adult; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D005786:Gene Expression Regulation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D015658:HIV Infections / Q000453:epidemiology / Q000276:immunology*; D006679:HIV Seropositivity; D015497:HIV-1 / Q000276:immunology*; D006239:Haplotypes; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008213:Lymphocyte Activation; D008297:Male; D008393:Marriage; D008875:Middle Aged; D011110:Polymorphism, Genetic; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D013019:South Africa; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: C584933:CCR5 protein, human; D007376:Interleukin-2; D019713:Receptors, CCR5; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: CCR5; HIV; immune activation; resistance