BACKGROUND: HIV infection in Africa is associated with immune activation and a cytokine profile that stimulates CCR5 expression. We investigated whether this immune activation is environmentally driven; if a dominant expression of CCR5 could indeed be detected in African individuals; and if R5 HIV strains would be prevalent in this population. METHODS: Freshly drawn peripheral blood mononuclear cells from HIV-uninfected African and Italian individuals living in rural Africa, from HIV-uninfected Africans and Italians living in Italy, and from HIV-infected African and Italian patients were analysed. Determinations of HIV coreceptor-specific mRNAs and immunophenotype analyses were performed in all samples. Virological analyses included virus isolation and characterization of plasma neutralizing activity. FINDINGS: Results showed that: immune activation is detected both in Italian and African HIV-uninfected individuals living in Africa but not in African subjects living in Italy; CCR5-specific mRNA is augmented and the surface expression of CCR5 is increased in African compared with Italian residents (CXCR4-specific mRNA is comparable); R5-HIV strains are isolated prevalently from lymphocytes of African HIV-infected patients; and plasma neutralizing activity in HIV-infected African patients is mostly specific for R5 strains. CONCLUSIONS: Immune activation in African residents is environmentally driven and not genetically predetermined. This immune activation results in a skewing of the CCR5 : CXCR4 ratio which is associated with a prevalent isolation of R5 viruses. These data suggest that the selection of the predominant virus strain within the population could be influenced by an immunologically driven pattern of HIV co receptor expression.
BACKGROUND:HIV infection in Africa is associated with immune activation and a cytokine profile that stimulates CCR5 expression. We investigated whether this immune activation is environmentally driven; if a dominant expression of CCR5 could indeed be detected in African individuals; and if R5 HIV strains would be prevalent in this population. METHODS: Freshly drawn peripheral blood mononuclear cells from HIV-uninfected African and Italian individuals living in rural Africa, from HIV-uninfected Africans and Italians living in Italy, and from HIV-infected African and Italian patients were analysed. Determinations of HIV coreceptor-specific mRNAs and immunophenotype analyses were performed in all samples. Virological analyses included virus isolation and characterization of plasma neutralizing activity. FINDINGS: Results showed that: immune activation is detected both in Italian and African HIV-uninfected individuals living in Africa but not in African subjects living in Italy; CCR5-specific mRNA is augmented and the surface expression of CCR5 is increased in African compared with Italian residents (CXCR4-specific mRNA is comparable); R5-HIV strains are isolated prevalently from lymphocytes of African HIV-infectedpatients; and plasma neutralizing activity in HIV-infected African patients is mostly specific for R5 strains. CONCLUSIONS: Immune activation in African residents is environmentally driven and not genetically predetermined. This immune activation results in a skewing of the CCR5 : CXCR4 ratio which is associated with a prevalent isolation of R5 viruses. These data suggest that the selection of the predominant virus strain within the population could be influenced by an immunologically driven pattern of HIV co receptor expression.
Authors: A Kassu; A Tsegaye; B Petros; D Wolday; E Hailu; T Tilahun; B Hailu; M T Roos; A L Fontanet; D Hamann; T F De Wit Journal: Clin Diagn Lab Immunol Date: 2001-11
Authors: Ilka Engelmann; Ulrike Moeller; Andrea Santamaria; Peter G Kremsner; Adrian J F Luty Journal: Immunology Date: 2006-09-20 Impact factor: 7.397
Authors: Jiri Mestecky; Peter F Wright; Lucia Lopalco; Herman F Staats; Pamela A Kozlowski; Zina Moldoveanu; Rashada C Alexander; Rose Kulhavy; Claudia Pastori; Leonard Maboko; Gabriele Riedner; Yuwei Zhu; Terri Wrinn; Michael Hoelscher Journal: AIDS Res Hum Retroviruses Date: 2010-11-22 Impact factor: 2.205
Authors: Peter W Hunt; Huyen L Cao; Conrad Muzoora; Isaac Ssewanyana; John Bennett; Nneka Emenyonu; Annet Kembabazi; Torsten B Neilands; David R Bangsberg; Steven G Deeks; Jeffrey N Martin Journal: AIDS Date: 2011-11-13 Impact factor: 4.177