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. DESIGN/ 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.
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. DESIGN/ 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: Thomas C Friedrich; Laura E Valentine; Levi J Yant; Eva G Rakasz; Shari M Piaskowski; Jessica R Furlott; Kimberly L Weisgrau; Benjamin Burwitz; Gemma E May; Enrique J León; Taeko Soma; Gnankang Napoe; Saverio V Capuano; Nancy A Wilson; David I Watkins Journal: J Virol Date: 2007-01-24 Impact factor: 5.103
Authors: Jane C Yaciuk; Matthew Skaley; Wilfried Bardet; Fredda Schafer; Danijela Mojsilovic; Steven Cate; Christopher J Stewart; Curtis McMurtrey; Kenneth W Jackson; Rico Buchli; Alex Olvera; Samandhy Cedeño; Montserrat Plana; Beatriz Mothe; Christian Brander; John T West; William H Hildebrand Journal: J Virol Date: 2014-08-27 Impact factor: 5.103
Authors: Norman L Letvin; Srini S Rao; Vi Dang; Adam P Buzby; Birgit Korioth-Schmitz; Dilani Dombagoda; Jenny G Parvani; Ryon H Clarke; Liat Bar; Kevin R Carlson; Pamela A Kozlowski; Vanessa M Hirsch; John R Mascola; Gary J Nabel Journal: J Virol Date: 2007-08-08 Impact factor: 5.103
Authors: Emily C Speelmon; Devon Livingston-Rosanoff; Anthony L Desbien; Jean Lee; W David Wick; Florian Hladik; M Juliana McElrath Journal: AIDS Res Hum Retroviruses Date: 2008-11 Impact factor: 2.205
Authors: Adam J Ritchie; Suzanne L Campion; Jakub Kopycinski; Zoe Moodie; Z Maggie Wang; Kruti Pandya; Stephen Moore; Michael K P Liu; Simon Brackenridge; Kristin Kuldanek; Kenneth Legg; Myron S Cohen; Eric L Delwart; Barton F Haynes; Sarah Fidler; Andrew J McMichael; Nilu Goonetilleke Journal: J Virol Date: 2011-01-26 Impact factor: 5.103
Authors: Michael A Eller; Bonnie M Slike; Josephine H Cox; Emil Lesho; Zhining Wang; Jeffrey R Currier; Janice M Darden; Victoria R Polonis; Maryanne T Vahey; Sheila Peel; Merlin L Robb; Nelson L Michael; Mary A Marovich Journal: PLoS One Date: 2011-09-16 Impact factor: 3.240