title: Correlates of resistance to HIV-1 infection in homosexual men with high-risk sexual behaviour.
abstract: OBJECTIVE
  To investigate possible correlates of HIV resistance in participants from the Amsterdam Cohort of Homosexual men who have remained HIV seronegative despite high-risk sexual behaviour.
  
  
  METHODS
  We studied in vitro HIV-1 susceptibility and adaptive and innate immunity in 29 high-risk seronegative (HRSN) and 15 HIV-negative pre-seroconversion (pre-SC) homosexual men from the same Amsterdam Cohort Study (ACS) who seroconverted to HIV-1 positive during active follow-up. Host genetics were compared between HRSN and HIV-positive ACS participants.
  
  
  RESULTS
  We found lower in vitro susceptibility for a CCR5-using (R5) HIV-1 variant, higher RANTES production levels, but no difference in coreceptor expression in HRSN as compared with pre-SC controls. Reduced R5 in vitro susceptibility of two HRSN tested was restored to normal levels by addition of antibodies against beta-chemokines. A higher proportion of HRSN carried the SDF-1 3'A variant and HLA-A*11, A*31 and Cw*15 alleles. ELIspot analysis with HIV-1 peptide stimulation revealed low frequencies of HIV-1-specific CD8 interferon-gamma producing cytotoxic T cells in both HRSN and pre-SC controls.
  
  
  CONCLUSIONS
  Low in vitro R5 susceptibility of cells from the HRSN men was due to beta-chemokine mediated inhibition of virus replication. The presence of HIV-1 specific cytotoxic T cells in both HRSN and pre-SC participants may signify exposure to the virus rather than protection from infection. Host genetic characteristics and other factors affecting innate immunity may contribute to differential resistance to HIV-1 infection among exposed seronegative individuals.
authors.affiliation: Department of Clinical Viro Immunology, Sanquin Research at CLB and Landsteiner Laboratory of the Academic Medical Centre, University of Amsterdam, The Netherlands.
authors.forename: Fransje A
authors.initials: FA
authors.lastname: Koning
authors.forename: Christine A
authors.initials: CA
authors.lastname: Jansen
authors.forename: Jos
authors.initials: J
authors.lastname: Dekker
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
authors.forename: Nicole
authors.initials: N
authors.lastname: Dukers
authors.forename: Debbie
authors.initials: D
authors.lastname: van Baarle
authors.forename: Maria
authors.initials: M
authors.lastname: Prins
authors.forename: Hanneke
authors.initials: H
authors.lastname: Schuitemaker
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018946:Chemokine CCL5 / Q000378:metabolism; D019742:Chemokines, CC / Q000378:metabolism; D004198:Disease Susceptibility / Q000821:virology; D005838:Genotype; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006579:Heterozygote; D018451:Homosexuality, Male; D006720:Homozygote; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D012189:Retrospective Studies; D012309:Risk-Taking
chemical_list: D018946:Chemokine CCL5; D019742:Chemokines, CC; D007371:Interferon-gamma