Present address: Women's Reproductive Health Research Center, Department of Obstetrics and Gynecology, Vanderbilt University Medical Center, Nashville, TN, USA.
Chemokine receptor expression in the human ectocervix: implications for infection by the human immunodeficiency virus-type I
Article first published online: 18 NOV 2004
Volume 113, Issue 4, pages 524–533, December 2004
How to Cite
Yeaman, G. R., Asin, S., Weldon, S., Demian, D. J., Collins, J. E., Gonzalez, J. L., Wira, C. R., Fanger, M. W. and Howell, A. L. (2004), Chemokine receptor expression in the human ectocervix: implications for infection by the human immunodeficiency virus-type I. Immunology, 113: 524–533. doi: 10.1111/j.1365-2567.2004.01990.x
- Issue published online: 18 NOV 2004
- Article first published online: 18 NOV 2004
- Received 15 March 2004; revised 17 August 2004; accepted 20 August 2004.
- chemokine receptor expression
Human immunodeficiency virus-type 1 (HIV-1) is a sexually transmitted pathogen that can infect cells in the female reproductive tract (FRT). The mechanism of viral transmission within the FRT and the mode of viral spread to the periphery are not well understood. To characterize the frequency of potential targets of HIV infection within the FRT, we performed a systematic study of the expression of HIV receptors (CD4, galactosyl ceramide (GalCer)) and coreceptors (CXCR4 and CCR5) on epithelial cells and leucocytes from the ectocervix. The ectocervix is a likely first site of contact with HIV-1 following heterosexual transmission, and expression of these receptors is likely to correlate with susceptibility to viral infection. We obtained ectocervical tissue specimens from women undergoing hysterectomy, and compared expression of these receptors among patients who were classified as being in the proliferative or secretory phases of their menstrual cycle at the time of hysterectomy, as well as from postmenopausal tissues. Epithelial cells from tissues at early and mid-proliferative stages of the menstrual cycle express CD4, although by late proliferative and secretory phases, CD4 expression was absent or weak. In contrast, GalCer expression was uniform in all stages of the menstrual cycle. CXCR4 expression was not detected on ectocervical epithelial cells and positive staining was only evident on individual leucocytes. In contrast, CCR5 expression was detected on ectocervical epithelial cells from tissues at all stages of the menstrual cycle. Overall, our results suggest that HIV infection of cells in the ectocervix could most likely occur through GalCer and CCR5. These findings are important to define potential targets of HIV-1 infection within the FRT, and for the future design of approaches to reduce the susceptibility of women to infection by HIV-1.