Abstract
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.
Highlights
HIV-1 male-to-female transmission occurs predominantly through vaginal intercourse and is mediated by semen [1]
Cervicovaginal and lymphoid tissues infected ex vivo with HIV-1 were cultured in the presence of IL-7 at concentrations of 5 or 25 ng/ mL, which are comparable with the concentrations of IL-7 found in semen of HIV-1-infected individuals [13]
Semen of HIV-1-infected individuals is highly enriched with IL-7, a crucial cytokine for the life cycle of CD4+ T cells, the primary target of HIV-1
Summary
HIV-1 male-to-female transmission occurs predominantly through vaginal intercourse and is mediated by semen [1]. Semen is more than a mere carrier of HIV-1, since it contains many biological factors that may facilitate or inhibit HIV-1 transmission [2,3]. Semen harbors distinct amyloidogenic peptides that enhance HIV infection and likely contribute to HIV transmission [4,5], and it contains cationic polypeptides that exhibit anti-HIV-1 activity [6]. Semen is rich in many cytokines [7] that may affect HIV-1 transmission [8,9,10,11]. Others, have previously reported that IL-7, one of the most prominent cytokines in semen of healthy fertile individuals [7], in seminal plasma can reach concentrations 100 times higher than in blood plasma [12,13]. In the course of HIV-1 infection the seminal plasma concentration of IL-7 is increased compared with that in uninfected individuals [12,13]
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