BACKGROUND: Overproduction of beta-chemokines and genetic variations in chemokine receptors have been correlated with protection against infection by HIV-1 or slow progression to AIDS in infected individuals. STUDY DESIGN AND METHODS: The protective role of chemokines and their receptors was evaluated in a group of seven uninfected (seronegative) hemophiliacs transfused with hemoderivatives presumably contaminated with HIV-1. This group was compared to a group of seven infected (seropositive) hemophiliacs and a group of healthy donors (controls). The CD4+ cell count, intracellular cytokine levels, beta-chemokine levels in plasma, beta-chemokine production by PBMNCs, and expression of chemokine receptors CCR5 and CXCR4 in CD4+ cells were evaluated. The occurrence of protective genotypes in CCR5, CCR2b, and SDF-1 (stromal cell-derived factor 1) genes and susceptibility to infection by HIV-1 were also studied. RESULTS: Significant differences in the production and plasma levels of beta-chemokines among the three groups were not detected. Lower IL-2 and IFN-gamma production was observed in the uninfected exposed hemophiliacs than in the controls. Genetic analysis of CCR5, CCR2b, and SDF-1 showed several polymorphisms associated with resistance in some HIV-exposed uninfected hemophiliacs. However, these genetic features cannot explain the protection of all exposed hemophiliacs. In fact, only one patient, carrying two copies of CCR5 from which 32 bp was deleted, showed low CCR5 expression and low susceptibility to infection by a CCR5-using HIV-1 strain. In contrast, PBMNCs from all other individuals supported infection in vitro by both CCR5- and CXCR4-using HIV-1 strains. CONCLUSION: It is not possible to assign to beta-chemo-kines and polymorphisms in chemokine receptors a central role in preventing HIV-1 infection. Natural protection against HIV-1 infection is likely to be due to a multiplicity of factors.
BACKGROUND: Overproduction of beta-chemokines and genetic variations in chemokine receptors have been correlated with protection against infection by HIV-1 or slow progression to AIDS in infected individuals. STUDY DESIGN AND METHODS: The protective role of chemokines and their receptors was evaluated in a group of seven uninfected (seronegative) hemophiliacs transfused with hemoderivatives presumably contaminated with HIV-1. This group was compared to a group of seven infected (seropositive) hemophiliacs and a group of healthy donors (controls). The CD4+ cell count, intracellular cytokine levels, beta-chemokine levels in plasma, beta-chemokine production by PBMNCs, and expression of chemokine receptors CCR5 and CXCR4 in CD4+ cells were evaluated. The occurrence of protective genotypes in CCR5, CCR2b, and SDF-1 (stromal cell-derived factor 1) genes and susceptibility to infection by HIV-1 were also studied. RESULTS: Significant differences in the production and plasma levels of beta-chemokines among the three groups were not detected. Lower IL-2 and IFN-gamma production was observed in the uninfected exposed hemophiliacs than in the controls. Genetic analysis of CCR5, CCR2b, and SDF-1 showed several polymorphisms associated with resistance in some HIV-exposed uninfected hemophiliacs. However, these genetic features cannot explain the protection of all exposed hemophiliacs. In fact, only one patient, carrying two copies of CCR5 from which 32 bp was deleted, showed low CCR5 expression and low susceptibility to infection by a CCR5-using HIV-1 strain. In contrast, PBMNCs from all other individuals supported infection in vitro by both CCR5- and CXCR4-using HIV-1 strains. CONCLUSION: It is not possible to assign to beta-chemo-kines and polymorphisms in chemokine receptors a central role in preventing HIV-1 infection. Natural protection against HIV-1 infection is likely to be due to a multiplicity of factors.
Authors: Philippe Colin; Yann Bénureau; Isabelle Staropoli; Yongjin Wang; Nuria Gonzalez; Jose Alcami; Oliver Hartley; Anne Brelot; Fernando Arenzana-Seisdedos; Bernard Lagane Journal: Proc Natl Acad Sci U S A Date: 2013-05-21 Impact factor: 11.205
Authors: Jun Jin; Philippe Colin; Isabelle Staropoli; Evelyne Lima-Fernandes; Cécile Ferret; Arzu Demir; Sophie Rogée; Oliver Hartley; Clotilde Randriamampita; Mark G H Scott; Stefano Marullo; Nathalie Sauvonnet; Fernando Arenzana-Seisdedos; Bernard Lagane; Anne Brelot Journal: J Biol Chem Date: 2014-05-22 Impact factor: 5.157
Authors: Jérôme Lane; Paul J McLaren; Lucy Dorrell; Kevin V Shianna; Amanda Stemke; Kimberly Pelak; Stephen Moore; Johannes Oldenburg; Maria Teresa Alvarez-Roman; Anne Angelillo-Scherrer; Francoise Boehlen; Paula H B Bolton-Maggs; Brigit Brand; Deborah Brown; Elaine Chiang; Ana Rosa Cid-Haro; Bonaventura Clotet; Peter Collins; Sara Colombo; Judith Dalmau; Patrick Fogarty; Paul Giangrande; Alessandro Gringeri; Rathi Iyer; Olga Katsarou; Christine Kempton; Philip Kuriakose; Judith Lin; Mike Makris; Marilyn Manco-Johnson; Dimitrios A Tsakiris; Javier Martinez-Picado; Evelien Mauser-Bunschoten; Anne Neff; Shinichi Oka; Lara Oyesiku; Rafael Parra; Kristiina Peter-Salonen; Jerry Powell; Michael Recht; Amy Shapiro; Kimo Stine; Katherine Talks; Amalio Telenti; Jonathan Wilde; Thynn Thynn Yee; Steven M Wolinsky; Jeremy Martinson; Shehnaz K Hussain; Jay H Bream; Lisa P Jacobson; Mary Carrington; James J Goedert; Barton F Haynes; Andrew J McMichael; David B Goldstein; Jacques Fellay Journal: Hum Mol Genet Date: 2013-01-30 Impact factor: 6.150
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