Repertoire of chemokine receptor expression in the female genital tract: Implications for human immunodeficiency virus transmission

Bruce K. Patterson*, Alan Landay, Jan Andersson, Clark Brown, Homira Behbahani, Dan Jiyamapa, Zareefa Burki, Donna Stanislawski, Mary Ann Czerniewski, Patricia Garcia

*Corresponding author for this work

Research output: Contribution to journalArticle

181 Scopus citations

Abstract

Sexually transmitted diseases, genital ulcer disease, and progesterone therapy increase susceptibility to lentivirus transmission. Infection of cells by human immunodeficiency virus (HIV) is dependent on expression of specific chemokine receptors known to function as HIV co-receptors. Quantitative kinetic reverse transcription-polymerase chain reaction was developed to determine the in vivo expression levels of CCRS, CXCR4, CCR3, CCR2b, and the cytomegalovirus-encoded US28 in peripheral blood mononuclear cells and cervical biopsies from 12 women with and without sexually transmitted diseases, genital ulcer disease, and progesterone-predominant conditions. Our data indicate that CCR5 is the major HIV co-receptor expressed in the female genital tract, and CXCR4 is the predominantly expressed HIV co-receptor in peripheral blood. CCR5 mRNA expression in the ectocervix was 10-fold greater than CXCR4, 20-fold greater than CCR2b, and 100-fold greater than CCR3. In peripheral blood, CXCR4 expression was 1.5- fold greater than CCR5, 10-fold greater than CCR2b, and 15-fold greater than CCR3. US28 was not expressed in cervical tissue despite expression in peripheral blood mononuclear cells from five individuals. CCR5 was significantly increased (p < 0.02) in biopsies from women with sexually transmitted diseases and others who were progesterone predominant. In vitro studies demonstrate that progesterone increases CCRS, CXCR4, and CCR3 expression and decreases CCR2b expression in lymphocytes and monocytes/macrophages. Characterization of chemokine receptors at the tissue level provides important information in identifying host determinants of HIV- 1 transmission.

Original languageEnglish (US)
Pages (from-to)481-490
Number of pages10
JournalAmerican Journal of Pathology
Volume153
Issue number2
DOIs
StatePublished - Aug 1998

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Patterson, B. K., Landay, A., Andersson, J., Brown, C., Behbahani, H., Jiyamapa, D., Burki, Z., Stanislawski, D., Czerniewski, M. A., & Garcia, P. (1998). Repertoire of chemokine receptor expression in the female genital tract: Implications for human immunodeficiency virus transmission. American Journal of Pathology, 153(2), 481-490. https://doi.org/10.1016/S0002-9440(10)65591-5