Background:  HIV-1 transmission most commonly occurs across cervico-vaginal and intestinal mucosal surfaces during unprotected vaginal and anal intercourse. From these sites, HIV-1 spreads to lymphoid tissue. While at later stages of HIV-1 disease, CXCR4 utilizing viruses (X4) are often isolated in blood, HIV-1 viruses that use CCR5 (R5) predominate at the early stage. The high rate of rectal transmission, together with the prevalence of R5 isolates at the early stages of infection, suggest that the rectal mucosa might favor the infection by R5 over X4 viruses. We have investigated the susceptibility of human rectal mucosa explants to R5 and X4 infection and compared it to that of human tonsillar lymphoid tissue ex vivo.

Methods:  Sigmoidoscopic biopsies acquired from healthy volunteers were placed in culture on top of collagen sponge-gel at the air liquid interface and were experimentally infected by the prototypic X4 isolate LAI.04 or the prototypic R5 isolate SF162. Viral replication was evaluated by the accumulation of p24 antigen and by the quantification of viral RNA by real time PCR in supernatants. We analyzed, by flow cytometry, the lymphoid cellular composition in explants, the lymphocyte expression of CCR5 and CXCR4 and HIV-1 induced cell depletion.

Results:  We found that in gut mucosal explants, the number of CCR5⁺CD4⁺ T cells targets for R5 HIV-1 infection is 5-fold higher than in tonsillar lymphoid tissue; R5 HIV-1 replication was similarly increased in gut.

Conclusions:  Thus, rectal mucosa is more susceptible to R5 infection than lymphoid tissue. However, X4 HIV-1 readily replicate in rectal mucosa ex vivo, suggesting that the differential expression of coreceptors alone cannot account for the selective R5 transmission across the rectal mucosa in vivo