Ph.D. Candidate: Julie Martellini
Institution: Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, Florida
Expected Completion: Fall 2010
Ph.D. Title: Cationic antimicrobial peptides derived from human seminal plasma inhibit HIV-1 infection
Synopsis: HIV infection has become a worldwide epidemic over the past few decades; still, the mode of heterosexual transmission is not completely understood. Our research focuses on innate immunity, and the intrinsic antimicrobial peptides found in mucosal secretions that form our first line of defense against bacteria, viruses and fungi.
The first chapter of our story exhibits how HIV (black, caped dancer) infection of a target cell (white dancer) is inhibited by the abundant antimicrobial peptides (balloons & throw pillows) derived from seminal plasma (off-white backdrop). Most of these peptides are cationic, or positively charged, and are attracted to the overall negative charge of the HIV envelope. In chapter two, it is demonstrated how purified Prostatic Acid Phosphatase (PAP) peptides (dancers in red), which are derived from the prostate and fragmented in seminal plasma, have the ability to form amyloid fibrils or protein aggregates upon intense agitation with a thermomixer (the belly dancer). Other studies have recently shown how these PAP fibrils, when artificially formed and then added to cell assays, can enhance HIV infection of a target cell in vitro by decreasing the negative-negative repulsion between the target cell membrane and HIV envelope. Thus, in chapter three we demonstrate how fusion of HIV with the target cell readily occurs with the assistance of PAP fibrils. However, our studies have focused on the physiological irrelevance of this phenomenon, and have revealed that seminal plasma maintains its antiviral activity in the presence of PAP fibrils. Chapter four demonstrates how abundantly accessible seminal plasma derived protease (blue dancer) effectively cleaves the PAP fibrils, preventing their enhancement of HIV infection. Exposed to seminal plasma’s antimicrobial peptides, the HIV is inhibited before it can infect the target cell. The significant antiviral activity of human seminal plasma may help explain why the rate of heterosexual HIV transmission is 1-3 for every 1000 coital acts in healthy individuals.
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