OBJECTIVES: To investigate the role of the CC chemokine receptor 5 (CCR5) for parenteral transmission of HIV-1. DESIGN: The prevalence of the delta32 deletion within the CCR5 gene was determined in a cohort of 207 patients, who had received documented amounts of non-antibody-tested and non-inactivated clotting factor concentrate. METHODS: Chromosomal DNA of haemophiliacs was isolated from whole blood. A portion of the CCR5 gene spanning the delta32 deletion was amplified by PCR. The resulting DNA fragments were analysed by agarose gel electrophoresis. RESULTS: The rate of HIV-1 infection was correlated strongly with increasing amounts of inoculated clotting factor concentrate. None of the HIV-positive patients (n = 129) had the delta32/delta32 genotype, whereas 12 out of 78 HIV-negative haemophiliacs had the homozygous delta32 deletion. CONCLUSIONS: The delta32/delta32 genotype was highly protective against HIV-1 infection, even in patients who had received millions of non-inactivated clotting factor units. As it is likely that in the early 1980s plasma pools were contaminated not only with monocyte-tropic HIV-1 strains, CCR5 appears to be the major mediator of HIV-1 infection. Furthermore, we conclude that there must be other protective mechanisms in multiply exposed non-infected haemophiliacs who have wild-type CCR5.
OBJECTIVES: To investigate the role of the CC chemokine receptor 5 (CCR5) for parenteral transmission of HIV-1. DESIGN: The prevalence of the delta32 deletion within the CCR5 gene was determined in a cohort of 207 patients, who had received documented amounts of non-antibody-tested and non-inactivated clotting factor concentrate. METHODS: Chromosomal DNA of haemophiliacs was isolated from whole blood. A portion of the CCR5 gene spanning the delta32 deletion was amplified by PCR. The resulting DNA fragments were analysed by agarose gel electrophoresis. RESULTS: The rate of HIV-1 infection was correlated strongly with increasing amounts of inoculated clotting factor concentrate. None of the HIV-positivepatients (n = 129) had the delta32/delta32 genotype, whereas 12 out of 78 HIV-negative haemophiliacs had the homozygous delta32 deletion. CONCLUSIONS: The delta32/delta32 genotype was highly protective against HIV-1 infection, even in patients who had received millions of non-inactivated clotting factor units. As it is likely that in the early 1980s plasma pools were contaminated not only with monocyte-tropic HIV-1 strains, CCR5 appears to be the major mediator of HIV-1 infection. Furthermore, we conclude that there must be other protective mechanisms in multiply exposed non-infected haemophiliacs who have wild-type CCR5.
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: Scott A Tenenbaum; Cindy A Morris; Steve S Alexander; Harris E McFerrin; Robert F Garry; Cindy A Leissinger Journal: Virol J Date: 2005-08-17 Impact factor: 4.099