Interleukin-7 Facilitates HIV-1 Transmission to Cervico-Vaginal Tissue ex vivo

The majority of hiv-1 infections in women occur through vaginal intercourse,in which virus-containing semen is deposited on the cervico-vaginal mucosa. semen is more than a mere carrier of hiv-1,since it contains many biological factors,in particular cytokines,that may affect hiv-1 transmission. the concentration of interleukin (il)-7,one of the most prominent cytokines in semen of healthy individuals,is further increased in semen of hiv-1-infected men. here,we investigated the potential role of il-7 in hiv-1 vaginal transmission in an ex vivo system of human cervico-vaginal tissue. we simulated an in vivo situation by depositing hiv-1 on cervico-vaginal tissue in combination with il-7 at concentrations comparable with those measured in semen of hiv-1-infected individuals. we found that il-7 significantly enhanced virus replication in ex vivo infected cervico-vaginal tissue. similarly,we observed an enhancement of hiv-1 replication in lymphoid tissue explants. analysis of t cells isolated from infected tissues showed that il-7 reduced cd4+ t cell depletion preventing apoptosis,as shown by the decrease in the number of cells expressing the apoptotic marker apo2.7 and the increase in the expression of the anti-apoptotic protein b-cell lymphoma (bcl)-2. also,il-7 increased the fraction of cycling cd4+ t cells,as evidenced by staining for the nuclear factor ki-67. high levels of seminal il-7 in vivo may be relevant to the survival of the founder pool of hiv-1-infected cells in the cervico-vaginal mucosa at the initial stage of infection,promoting local expansion and dissemination of hiv infection.