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Impact of semen on mucosal transmission of HIV

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Author	Balandya, Emmanuel C.
Title	Impact of semen on mucosal transmission of HIV
Date	2012
Abstract	Semen is the major vector for sexual transmission of HIV worldwide, yet little is known about its role in modulating mucosal transmission of HIV. Understanding the impact of semen on mucosal transmission of HIV could open up novel means of preventing the sexual transmission of HIV. To understand how human semen modulates female reproductive tract susceptibility to HIV infection, we collected human semen from healthy donors after informed consent and separated seminal plasma from spermatozoa via centrifugation. Using post-hysterectomy human female reproductive tract epithelial cells and peripheral blood mononuclear cells, we investigated the impact of seminal plasma on the phenotype, activity and HIV infectivity of the female reproductive tract epithelial cells, CD4+ regulatory T cells and the primary cellular targets of HIV infection, the CD4+ T cells. In cells from the female reproductive tract, seminal plasma enhanced the epithelial cell barrier function and reduced the epithelial cell secretion of RANTES and IL-6. In CD4+ T cells, seminal plasma promoted the non-proliferative expansion of CD4+ regulatory T cells with enhanced suppressive function via increased secretion of the immunosuppressive cytokine TGF- ?. Seminal plasma reduced CD4+ T cell surface expression of the HIV receptor CD4, activation and proliferation and protected CD4+ T cells from infection with both, X4 and R5 tropic HIV. Conversely, the seminal plasma-mediated increase in the female reproductive tract epithelial cell and CD4+ T cell surface expression of the HIV co-receptor CCR5 mitigated its protective effects, contributing to the preferential infection by the R5 tropic HIV. The observed seminal plasma protection of CD4+ T cells from HIV infection was mediated by heat stable seminal plasma components of intermediate molecular weight. These data suggest that human semen impacts the barrier integrity and immune responses by both the epithelial cells and CD4+ T cells in the female reproductive tract and accounts for both the relative inefficiency and preferential transmission of R5 tropic HIV. The rich intermediate molecular weight components of seminal plasma mediate CD4+ T cell protection from HIV infection. These findings have the potential to lead to the development of novel approaches to prevent the ongoing global sexual transmission of HIV.
Description	xxi, 161 leaves : ill. (some col.) ; 28 cm.
Format	application/pdf
Advisor	Lahey, Timothy P.; Wira, Charles R.; Martin, Kathleen A.; Connor, Ruth I.
College	Dartmouth College -- Experimental and Molecular Medicine Program. Dartmouth Medical School.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.415

Title	Page 1
Format	application/pdf
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Full Text	IMPACT OF SEMEN ON MUCOSAL TRANSMISSION OF HIV A Thesis Submitted to the Faculty in partial fulfillment of the requirements for the degree of Doctor of Philosophy In Experimental and Molecular Medicine By Emmanuel C. Balandya DARTMOUTH COLLEGE Hanover, New Hampshire May, 2012 Examining Committee: ________________________________ (Chair) Timothy P. Lahey, MD, MMSc ________________________________ Charles R. Wira, Ph.D. ________________________________ Kathleen A. Martin, Ph.D. ________________________________ Ruth I. Connor, Ph.D. ____________________________ Brian W. Pogue, Ph.D. Dean of Graduate Studies

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Impact of semen on mucosal transmission of HIV

Impact of semen on mucosal transmission of HIV