Interleukin-7 HIV Transmission to Cervico-Vaginal Tissue in vivo



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Abstract

The majority of HIV-1 infections in women transmit 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.

Full Text

Интерлейкин-7 способствует переносу ВИЧ-1 на цервиковагиналь-ную ткань in vivo
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About the authors

A. Introini

Eunice Kennedy-Shriver National Institute of ChildHealth andHuman Development; University of Milan

Bethesda, Maryland, United States of America, 31 Center Drive Building 31, Room 2A32 Bethesda, MD 20892-2425; Via Festa del Perdono, 12 - 20122, Milan, Italy

C. Vanpouille

Eunice Kennedy-Shriver National Institute of ChildHealth andHuman Development

Bethesda, Maryland, United States of America, 31 Center Drive Building 31, Room 2A32 Bethesda, MD 20892-2425

A. Lisco

Eunice Kennedy-Shriver National Institute of ChildHealth andHuman Development

Bethesda, Maryland, United States of America, 31 Center Drive Building 31, Room 2A32 Bethesda, MD 20892-2425

J. -C Grivel

Eunice Kennedy-Shriver National Institute of ChildHealth andHuman Development

Bethesda, Maryland, United States of America, 31 Center Drive Building 31, Room 2A32 Bethesda, MD 20892-2425

L. Borisovich Margolis

Eunice Kennedy-Shriver National Institute of ChildHealth andHuman Development

Email: margolis@helix.nih.gov
Bethesda, Maryland, United States of America, 31 Center Drive Building 31, Room 2A32 Bethesda, MD 20892-2425

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