OBJECTIVES: To test the hypothesis that in comparison with those with shorter risk duration, individuals with longer HIV risk duration would have reduced susceptibility to HIV-1 infection as measured by CCR5 expression, and to evaluate whether variation in CCR5 expression could be explained by known genetic polymorphisms. DESIGN AND METHODS: A cross-sectional study of HIV-1 exposed but uninfected men who have sex with men. The risk duration was estimated from self-reported years since first receptive anal intercourse. CCR5 expression on peripheral blood CD4+ monocytes and T cells was determined by flow cytometry. The CCR5-Delta32 mutation and polymorphisms in the CCR5 promoter and CCR2 as well as the copy number of CCL3L1 were analyzed by polymerase chain reaction. Plasma levels of MIP-1alpha (CCL3), MIP-1beta (CCL4) and RANTES (CCL5) were also measured. As risk duration varied with age, analyses were restricted to 67 individuals aged 30-49 years. RESULTS: Multiple linear regression analyses, adjusted for age and race, showed a significant negative association between HIV risk duration and CCR5 expression on monocytes (P = 0.01), and in a separate model, a similar negative association with CCR5 expression on T cells (P = 0.03). Low CCR5 expression was attributable mainly to CCR5-Delta32 heterozygosity and the CCR5-59029G allele. CONCLUSIONS: We confirmed a role for reduced CCR5 expression in HIV-1 resistance. CCR5-Delta32 heterozygosity and the CCR5-59029G allele were significant predictors of low CCR5 expression. Individuals with high CCR5 expression who resisted infection despite long HIV risk duration form an interesting group within which to search for additional mechanisms of resistance to HIV infection.
OBJECTIVES: To test the hypothesis that in comparison with those with shorter risk duration, individuals with longer HIV risk duration would have reduced susceptibility to HIV-1 infection as measured by CCR5 expression, and to evaluate whether variation in CCR5 expression could be explained by known genetic polymorphisms. DESIGN AND METHODS: A cross-sectional study of HIV-1 exposed but uninfected men who have sex with men. The risk duration was estimated from self-reported years since first receptive anal intercourse. CCR5 expression on peripheral blood CD4+ monocytes and T cells was determined by flow cytometry. The CCR5-Delta32 mutation and polymorphisms in the CCR5 promoter and CCR2 as well as the copy number of CCL3L1 were analyzed by polymerase chain reaction. Plasma levels of MIP-1alpha (CCL3), MIP-1beta (CCL4) and RANTES (CCL5) were also measured. As risk duration varied with age, analyses were restricted to 67 individuals aged 30-49 years. RESULTS: Multiple linear regression analyses, adjusted for age and race, showed a significant negative association between HIV risk duration and CCR5 expression on monocytes (P = 0.01), and in a separate model, a similar negative association with CCR5 expression on T cells (P = 0.03). Low CCR5 expression was attributable mainly to CCR5-Delta32 heterozygosity and the CCR5-59029G allele. CONCLUSIONS: We confirmed a role for reduced CCR5 expression in HIV-1 resistance. CCR5-Delta32 heterozygosity and the CCR5-59029G allele were significant predictors of low CCR5 expression. Individuals with high CCR5 expression who resisted infection despite long HIV risk duration form an interesting group within which to search for additional mechanisms of resistance to HIV infection.
Authors: Janelle R Salkowitz; Shannon E Bruse; Howard Meyerson; Hernan Valdez; Donald E Mosier; Clifford V Harding; Peter A Zimmerman; Michael M Lederman Journal: Clin Immunol Date: 2003-09 Impact factor: 3.969
Authors: M Samson; F Libert; B J Doranz; J Rucker; C Liesnard; C M Farber; S Saragosti; C Lapoumeroulie; J Cognaux; C Forceille; G Muyldermans; C Verhofstede; G Burtonboy; M Georges; T Imai; S Rana; Y Yi; R J Smyth; R G Collman; R W Doms; G Vassart; M Parmentier Journal: Nature Date: 1996-08-22 Impact factor: 49.962
Authors: L Wu; W A Paxton; N Kassam; N Ruffing; J B Rottman; N Sullivan; H Choe; J Sodroski; W Newman; R A Koup; C R Mackay Journal: J Exp Med Date: 1997-05-05 Impact factor: 14.307
Authors: Gabriel Catano; Zoya A Chykarenko; Andrea Mangano; J-M Anaya; Weijing He; Alison Smith; Rosa Bologna; Luisa Sen; Robert A Clark; Andrew Lloyd; Ludmila Shostakovich-Koretskaya; Sunil K Ahuja Journal: J Infect Dis Date: 2011-01-15 Impact factor: 5.226
Authors: Weijing He; John Castiblanco; Elizabeth A Walter; Jason F Okulicz; Sunil K Ahuja Journal: Curr Opin HIV AIDS Date: 2010-11 Impact factor: 4.283
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: Brandon L Walter; Andrew E Armitage; Stephen C Graham; Tulio de Oliveira; Peter Skinhøj; E Yvonne Jones; David I Stuart; Andrew J McMichael; Bruce Chesebro; Astrid Kn Iversen Journal: AIDS Date: 2009-06-01 Impact factor: 4.177
Authors: Hemant Kulkarni; Brian K Agan; Vincent C Marconi; Robert J O'Connell; Jose F Camargo; Weijing He; Judith Delmar; Kenneth R Phelps; George Crawford; Robert A Clark; Matthew J Dolan; Sunil K Ahuja Journal: PLoS One Date: 2008-09-08 Impact factor: 3.240