HIV-1 sexual transmission: early events of HIV-1 infection of human cervico-vaginal tissue in an optimized ex vivo model

Infection and dissemination of HIV-1 through the female body after vaginal intercourse depends on the activation/differentiation status of mucosal CD4 T cells. Here, we investigated this status and the susceptibility to HIV-1 infection of human cervico-vaginal tissue ex vivo. We found that virtually all T cells are of the effector memory phenotype with broad CCR5 expression. As it does in vivo, human cervico-vaginal tissue ex vivo preferentially supports the productive infection of R5 HIV-1 rather than that of X4 HIV-1 in spite of broad expression of CXCR4. X4 HIV-1 replicated only in the few tissues that were enriched in CD27(+)CD28(+) effector memory CD4 T cells. Productive infection of R5 HIV-1 occurred preferentially in activated CD38(+)CD4 T cells and was followed by a similar activation of HIV-1-uninfected (bystander) CD4 T cells that may amplify viral infection. These results provide new insights into the dependence of HIV-1 infection and dissemination on the activation/differentiation of cervico-vaginal lymphocytes.