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

Andrea Introini, Christophe Vanpouille, Andrea Lisco, Jean-Charles B. Grivel, Leonid Margolis

Research output: Contribution to journalArticle

33 Citations (Scopus)

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.

Original languageEnglish
Article numbere1003148
JournalPLoS Pathogens
Volume9
Issue number2
DOIs
Publication statusPublished - Feb 2013
Externally publishedYes

Fingerprint

Interleukin-7
HIV-1
Semen
T-Lymphocytes
HIV Infections
Mucous Membrane
Cytokines
Apoptosis Regulatory Proteins
Biological Factors
B-Cell Lymphoma
Lymphoid Tissue
Virus Replication
Cell Count
Apoptosis
Staining and Labeling
Viruses
Survival

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

Cite this

Interleukin-7 Facilitates HIV-1 Transmission to Cervico-Vaginal Tissue ex vivo. / Introini, Andrea; Vanpouille, Christophe; Lisco, Andrea; Grivel, Jean-Charles B.; Margolis, Leonid.

In: PLoS Pathogens, Vol. 9, No. 2, e1003148, 02.2013.

Research output: Contribution to journalArticle

Introini, Andrea ; Vanpouille, Christophe ; Lisco, Andrea ; Grivel, Jean-Charles B. ; Margolis, Leonid. / Interleukin-7 Facilitates HIV-1 Transmission to Cervico-Vaginal Tissue ex vivo. In: PLoS Pathogens. 2013 ; Vol. 9, No. 2.
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