Human immunodeficiency virus receptor and coreceptor expression on human uterine epithelial cells: regulation of expression during the menstrual cycle and implications for human immunodeficiency virus infection

Authors

  • Grant R. Yeaman,

    1. Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN, USA and the Departments of Microbiology and Immunology, and
    Search for more papers by this author
  • Alexandra L. Howell,

    1. Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN, USA and the Departments of Microbiology and Immunology, and
    2. V.A. Medical Center, White River Junction, VT, USA
    Search for more papers by this author
  • Sally Weldon,

    1. Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN, USA and the Departments of Microbiology and Immunology, and
    Search for more papers by this author
  • Douglas J. Demian,

    1. Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN, USA and the Departments of Microbiology and Immunology, and
    Search for more papers by this author
  • Jane E. Collins,

    1. Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN, USA and the Departments of Microbiology and Immunology, and
    Search for more papers by this author
  • Denise M. O'Connell,

    1. Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN, USA and the Departments of Microbiology and Immunology, and
    Search for more papers by this author
  • Susana N. Asin,

    1. Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN, USA and the Departments of Microbiology and Immunology, and
    Search for more papers by this author
  • Charles R. Wira,

    1. Physiology, Dartmouth Medical School, Lebanon, NH, USA and
    Search for more papers by this author
  • Michael W. Fanger

    1. Department of Obstetrics and Gynecology, Vanderbilt University, Nashville, TN, USA and the Departments of Microbiology and Immunology, and
    Search for more papers by this author

Dr A. L. Howell, V.A. Medical Center, Research Service, 215 North Main St, White River Jct, VT 05009, USA. E-mail: Alexandra.L.Howell@Dartmouth.EDU

Summary

Human immunodeficiency virus-1 (HIV-1) is primarily a sexually transmitted disease. Identification of cell populations within the female reproductive tract that are initially infected, and the events involved in transmission of infection to other cells, remain to be established. In this report, we evaluated expression of HIV receptors and coreceptors on epithelial cells in the uterus and found they express several receptors critical for HIV infection including CD4, CXCR4, CCR5 and galactosylceramide (GalC). Moreover, expression of these receptors varied during the menstrual cycle. Expression of CD4 and CCR5 on uterine epithelial cells is high throughout the proliferative phase of the menstrual cycle when blood levels of oestradiol are high. In contrast, CXCR4 expression increased gradually throughout the proliferative phase. During the secretory phase of the cycle when both oestradiol and progesterone are elevated, CD4 and CCR5 expression decreased whereas CXCR4 expression remained elevated. Expression of GalC on endometrial glands is higher during the secretory phase than during the proliferative phase of the menstrual cycle. Because epithelial cells line the female reproductive tract and express HIV receptors and coreceptors, it is likely that they are one of the first cell types to become infected. The hormonal regulation of HIV receptor expression may affect a woman's susceptibility to HIV infection during her menstrual cycle. Moreover, selective coreceptor expression could account for the preferential transmission of R5-HIV-1 strains to women. In addition, these studies provide evidence that the uterus, and potentially the entire upper reproductive tract, are important sites for the initial events involved in HIV infection.

Ancillary