Microbicidal approaches to interdict virus infections in human epithelial cell cultures, organ tissue cultures and human epithelial xenografts
Year: 2008
Type: dissertation
Abstract: Sexually transmitted infections (STIs) are causing a hidden epidemic. Everyday infected individuals and their families quietly suffer physically, psychologically and financially. Worldwide, STIs are a major economic burden with direct medical costs for treating these diseases in United States alone is $15.3 billion per year. As with many diseases and infections, prevention is the key and with our current technology the best hope for prevention is microbicides. The work set forth in this thesis examined three vastly different microbicides each with very different modes for preventing the initial stages of HIV-1 infection. The prototypic SDS Hydrogel is a broad-spectrum microbicide. We show that our prototypic SDS Hydrogel has potent antiviral activity against enveloped (HIV-1 and HSV-2) and non-enveloped (HPV-11) sexually transmitted viruses. The second microbicide is comprised of a liposomal delivered short interfering RNA (siRNA) pool targeting human chemokine receptor 5 (CCR5). The down-regulation of CCR5 along with other molecules (gp340, syndecans, a4[beta]7 integrin), which allow HIV-1 to remain infectious, may potentially inhibit binding of R5 forms of HIV-1 from binding to the co-receptor, therefore, preventing the subsequent infection. Lastly, the recombinant L. plantarum secreting cyanovirin is a pro-biotic microbicide that decreased HIV-1 infectivity in vitro and we were able to recolonize human vaginal epithelia ex vivo and in vivo.
DOI: 10.17918/etd-3473
Authors: Veronica M. Holmes, Mary K. Howett
Institutions: University of Dhaka, Drexel University
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4206203248