Productive HIV-1 infection of human cervical tissue ex vivo is associated with the secretory phase of the menstrual cycle

Mucosal Immunol. 2013 Nov;6(6):1081-90. doi: 10.1038/mi.2013.2. Epub 2013 Feb 6.


Cervical tissue explants (CTEs) from 22 HIV-1 seronegative women were exposed to R5 HIV-1 ex vivo. Eight CTEs were productively infected in terms of HIV-1 p24Gag release in culture supernatants, whereas 14 were not. Nonetheless, both accumulation of HIV-1gag DNA and of p24Gag(+) CD4(+) T cells and macrophages occurred in both productive and, at lower levels, in nonproductive CTEs. Nonproductive CTEs differed from productive CTEs for higher secretion of C-C motif chemokine ligand 3 (CCL3) and CCL5. A post-hoc analysis revealed that all productive CTEs were established from women in their secretory phase of the menstrual cycle, whereas nonproductive CTEs were derived from women either in their secretory (28%) or proliferative (36%) menstrual cycle phases or with an atrophic endometrium (36%). Thus, our results support the epidemiological observation that sexual HIV-1 transmission from males to women as well as from women to men is more efficient during their secretory phase of the menstrual cycle.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • Cells, Cultured
  • Cervix Uteri / immunology*
  • Cervix Uteri / pathology
  • Cervix Uteri / virology
  • Chemokine CCL3 / metabolism
  • Chemokine CCL5 / metabolism
  • DNA, Viral / analysis
  • Female
  • HIV Core Protein p24 / metabolism
  • HIV Infections / immunology
  • HIV Infections / transmission*
  • HIV-1 / pathogenicity
  • HIV-1 / physiology*
  • Humans
  • Luteal Phase
  • Macrophages / immunology*
  • Macrophages / virology
  • Middle Aged
  • Organ Culture Techniques
  • Virulence


  • Chemokine CCL3
  • Chemokine CCL5
  • DNA, Viral
  • HIV Core Protein p24