CCR5 HIV-1 receptor predominance in adult male prepuce; the major entry route for HIV-1 in indigenous black males in zambia?

Abstract

HIV-1 entry requires not only CD4 molecule but also CCR5 (CD 195) and CXCR4 (CD 184) coreceptors. A number of randomised controlled trials in Africa have reported that male circumcision (MC) reduces the risk of HIV-1 acquisition by up to 60%. Other studies have reported that sexually transmitted infections (STIs) increase the risk of infection by HIV via an inflammatory  recruitment of more HIV target cells to the foreskin. Our aim was to compare the density of HIV-1 co-receptors (CCR5 and CXCR4) in naïve penile prepuce of neonates and penile prepuce of adults with and without history of ulcerative STIs at Male Circumcision Centres in Lusaka, Zambia. Twenty (20) fresh foreskin samples were included: five (5) from neonates, ten (10) from adult males without history of ulcerative STIs and five (5) from adult males with a history of ulcerative STIs. Immediately following MC, fresh foreskin specimens were fixed using 10% normal buffered formalin and transported to University Teaching Hospital (UTH) where tissues were processed and stained with anti-CD 195 and anti-CD 184 antibodies. Neonatal penile foreskin co-receptor mean density for CCR5 and CXCR4 was  13±5.148/mm2 and 7±1.581/mm2 respectively. CCR5 mean density of adults without past history of ulcerative STIs was 42.1±11.874/mm2 while those with history of ulcerative STIs was 78.6±13.520/mm2. Densities of CCR5 were all statistically  significant with both having Pvalue of 0.000. CXCR4 mean density was 18.6±4.812/mm2 in adults without past history of
ulcerative STIs and 23.4±4.393/mm2 in those with history of ulcerative STIs giving an insignificant P-value of 0.084. It could be concluded that CCR5 co-receptors provide major entry route for HIV-1 in male adults and that CCR5 seemed to be mobilized more than CXCR4 to the prepuce during inflammation. This supports evidence that MC reduces CCR5 co-receptors for acquisition and transmission of R5 strains of HIV-1.

Key words: HIV, CCR5, CD 195, CD 184.