Global Expression of Molecular Transporters in the Human Vaginal Tract: Implications for HIV Chemoprophylaxis

Manjula Gunawardana, Madeline Mullen, John A. Moss, Richard B. Pyles, Rebecca J. Nusbaum, Jignesh Patel, Kathleen L. Vincent, Charles Wang, Chao Guo, Yate Ching Yuan, Charles D. Warden, Marc M. Baum

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Background:Pre-exposure chemoprophylaxis (PrECP) using antiretroviral agents is a promising strategy for the prevention of sexual HIV transmission in women. Molecular transporters in the human vaginal tract (VT) may play a pivotal role in determining drug disposition and, consequently, pharmacodynamic outcomes in these efforts. Little is known, however, on the expression of these transporters in vaginal tissues, representing a critical knowledge gap.Methodology/Principal Findings:Our study analyzed the genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women undergoing gynecologic surgeries. The analysis revealed that, unexpectedly, a large number (43%) of gene isoforms corresponding to membrane transporters were over-expressed (above the median expression level) in all samples. A subset of 12 highly expressed membrane transporters was identified and contained 10 members (83%) of the solute carrier superfamily. The largest difference in membrane transporter gene expression was observed across subjects, but more subtle differential expression also was found along the anterior-posterior axis of the VT. Cross-validation of the microarray analyses with measurements RT-qPCR demonstrated high concordance between these data sets. Immunofluorescence labeling of membrane transporter proteins in vaginal tissues was highly dependent on tissue/cell types.Conclusions/Significance:Antiretroviral PrECP drugs currently under evaluation are substrates for molecular transporters that were commonly expressed, but fell into both over- or under-expressed categories in all samples, suggesting a complex role for carrier-mediated processes in determining the disposition of these xenobiotics in vaginal tissues. These findings hold important implications for the successful development of products, either oral or intravaginal, for female-controlled HIV PrECP.

Original languageEnglish (US)
Article numbere77340
JournalPloS one
Volume8
Issue number10
DOIs
StatePublished - Oct 15 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Gunawardana, M., Mullen, M., Moss, J. A., Pyles, R. B., Nusbaum, R. J., Patel, J., Vincent, K. L., Wang, C., Guo, C., Yuan, Y. C., Warden, C. D., & Baum, M. M. (2013). Global Expression of Molecular Transporters in the Human Vaginal Tract: Implications for HIV Chemoprophylaxis. PloS one, 8(10), [e77340]. https://doi.org/10.1371/journal.pone.0077340