Interleukin-7 facilitates HIV-1 transmission to cervico-vaginal tissue ex vivo

PLoS Pathog. 2013 Feb;9(2):e1003148. doi: 10.1371/journal.ppat.1003148. Epub 2013 Feb 7.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Apoptosis
  • Apoptosis Regulatory Proteins / metabolism
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / virology
  • Cell Proliferation
  • Cervix Uteri / virology*
  • Female
  • Gene Expression Regulation, Viral
  • HIV Infections / transmission*
  • HIV Infections / virology
  • HIV-1 / physiology*
  • Humans
  • Interleukin-7 / metabolism*
  • Ki-67 Antigen / metabolism
  • Lymphoid Tissue / virology
  • Male
  • Molecular Sequence Data
  • Palatine Tonsil / virology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Recombinant Proteins
  • Vagina / virology*
  • Virus Replication


  • Apoptosis Regulatory Proteins
  • Interleukin-7
  • Ki-67 Antigen
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins

Associated data

  • UniProtKB/P10415
  • UniProtKB/P13232
  • UniProtKB/P46013
  • UniProtKB/Q7ZBG8