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.

HIV-1 infection results in an aberrant production of cytokines and reactivation of EBV and CMV that further changes the seminal cytokine network. The altered seminal milieu in HIV-1 infection may be a determinant of HIV-1 sexual transmission.

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Cervical tissue explants (CTE) from 22 HIV-1 seronegative women were exposed to R5 HIV-1 ex vivo. Eight CTE were productively infected in terms of HIV-1 p24Gag release in culture supernatants whereas 14 were not. Nonetheless, both accumulation of HIV-1gag DNA and of p24Gag+ CD4+ T cells and macrophages occurred in both productive and, at lower levels, in nonproductive CTE. Nonproductive CTE differed from productive CTE for higher secretion of CCL3 and CCL5. A post-hoc analysis revealed that all productive CTE were established from women in their secretory phase of the menstrual cycle, whereas nonproductive CTE derived from women either in their secretory (28%) or proliferative (36%) menstrual cycle phases or with an atrophic endometrium (36%). Thus, our results support the epidemiological observation that sexual HIV-1 transmission from males to women as well as from women to men is more efficient during their secretory phase of the menstrual cycle.