Mechanisms of sexual transmission of enveloped viruses and a novel strategy to prevent infection.
Item
-
Title
-
Mechanisms of sexual transmission of enveloped viruses and a novel strategy to prevent infection.
-
Identifier
-
AAI9820595
-
identifier
-
9820595
-
Creator
-
Zacharopoulos, Vanaja Rao.
-
Contributor
-
Adviser: Richard Coico
-
Date
-
1998
-
Language
-
English
-
Publisher
-
City University of New York.
-
Subject
-
Biology, Cell | Health Sciences, Pathology | Health Sciences, Public Health
-
Abstract
-
Heterosexual transmission of HIV accounts for the vast majority of AIDS cases in the world. An important factor compounding this problem is the occurrence of sexually transmitted diseases which facilitate the transmission of HIV. There has been increasing interest in the development of female-controlled prevention methods especially since the likelihood of a vaccine against HIV seems to be remote and probably beyond the reach of people who are at greatest need for protection.;In this thesis I have approached the issue of developing a vaginal microbicide by using both in vitro systems and animal models. Initial experiments were performed to understand how viral pathogens can be transmitted in the female genital tract, specifically by addressing the question of whether infected cells originating from semen can penetrate the mucosal barrier of the vagina. By tracking the migration of labelled autologous blood cells from the mouse vagina, cells were found beneath the epithelium and in neighboring lymph nodes a few hours after vaginal inoculation. Using an in vitro model for the sexual transmission of the human retrovirus, Human T Lymphotropic Virus Type I, mechanisms of cell to cell adhesion and infection were studied. Certain sulfated polysaccharides were found to block both adhesion of infected cells to target cells as well as subsequent infection. In order to test the efficacy of these compounds in blocking genital infection in vivo, I developed a mouse model for the vaginal transmission of HTLV-I. Although mice were infected by this route, as evidenced by the presence of proviral DNA in spleen cells, the model is not ready for efficient testing of potential antiviral compounds. The mouse model for genital herpes was used to test the ability of candidate compounds to block infection of Herpes Simplex Virus-2 via the vaginal route. The sulfated polysaccharide Carrageenan was highly effective in protecting mice from infection. Antimicrobial peptides were also found to block infection.;The research performed here shows that the development of a vaginal microbicide to protect women against HIV and possibly other sexually transmitted viruses is a feasible and realistic goal. Such a formulation should be able to block free virus as well as virus-infected cells from contact with the target cells in the vagina and/or cervix. More animal models are needed to further verify the antiviral activity of potential compounds.
-
Type
-
dissertation
-
Source
-
PQT Legacy CUNY.xlsx
-
degree
-
Ph.D.
