title: Interleukin-7 facilitates HIV-1 transmission to cervico-vaginal tissue ex vivo.
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.
authors: Eunice Kennedy-Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, United States of America.
authors: Andrea
authors: A
authors: Introini
authors: Christophe
authors: C
authors: Vanpouille
authors: Andrea
authors: A
authors: Lisco
authors: Jean-Charles
authors: JC
authors: Grivel
authors: Leonid
authors: L
authors: Margolis
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000821:virology; D049109:Cell Proliferation; D002584:Cervix Uteri / Q000821:virology*; D005260:Female; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000635:transmission* / Q000821:virology; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D008221:Lymphoid Tissue / Q000821:virology; D008297:Male; D008969:Molecular Sequence Data; D014066:Palatine Tonsil / Q000821:virology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011994:Recombinant Proteins; D014621:Vagina / Q000821:virology*; D014779:Virus Replication
chemical_list: D051017:Apoptosis Regulatory Proteins; D015851:Interleukin-7; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins