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

• Published in: PLoS pathogens Vol. 9; no. 2; p. e1003148
• Main Authors: Introini, Andrea, Vanpouille, Christophe, Lisco, Andrea, Grivel, Jean-Charles, Margolis, Leonid
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.02.2013; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; Apoptosis; Apoptosis Regulatory Proteins - metabolism; Biology; CD4-Positive T-Lymphocytes - cytology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - virology; Cell Proliferation; Cervix Uteri - virology; Colleges & universities; Disease transmission; Experiments; Female; Gene Expression Regulation, Viral; Health aspects; HIV; HIV infection; HIV Infections - transmission; HIV Infections - virology; HIV-1 - physiology; Human immunodeficiency virus; Humans; Interleukin-7 - metabolism; Interleukins; Ki-67 Antigen - metabolism; Lymphocytes; Lymphoid Tissue - virology; Lymphoma; Male; Medicine; Molecular Sequence Data; Palatine Tonsil - virology; Physiological aspects; Plasma; Proteins; Proto-Oncogene Proteins c-bcl-2 - metabolism; Recombinant Proteins; Sexual intercourse; Statistical analysis; Tissues; Vagina - virology; Virus Replication; Italy; HIV Infections; HIV-1; Cell Proliferation; Humans; Molecular Sequence Data; Vagina; Male; Recombinant Proteins; Cervix Uteri; Interleukin-7; Lymphoid Tissue; Palatine Tonsil; Apoptosis Regulatory Proteins; Virus Replication; Gene Expression Regulation, Viral; Ki-67 Antigen; Female; CD4-Positive T-Lymphocytes; Proto-Oncogene Proteins c-bcl-2; Apoptosis
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1003148

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.