Grant: CIHR Fellowship

Many viruses trigger the blood clotting system in an infected person, causing a wide range of clinical complications; from heart disease to bleeding. A breakthrough was made by the Pryzdial lab who showed that clotting activators are hijacked by these germs to not only contribute to clotting, but also increase infection. My project focuses on the lab's discovery that a protein called, tissue factor, is integrated into the virus' surface. Tissue factor is found within our cell membranes and is essential for 1) initiation of blood coagulation and 2) activation of critical cell functions. Many viruses are covered with a membrane, called an envelope, which is acquired from the infected cells and can therefore contain tissue factor. Here we propose to study tissue factor on HIV, which is a major global problem and thrombosis is a primary challenge to these patients' life expectancy. I will take biochemical and model animal approaches to extend the lab's preliminary data that shows tissue factor is on HIV. An unambiguous evaluation of the role of tissue factor will be made by creating sister cell lines with state-of-the-art CRISPR gene editing that either do or do not have tissue factor, thereby enabling us to propagate and purify HIV that either does or does not have tissue factor, as the lab has done previously for oral herpes. Then enzyme kinetics measurements to confirm tissue factor function and biological experiments in mice to determine effects on infection will be conducted. In addition to HIV, the Pryzdial lab has preliminary data for five virus types that supports the hypothesis that any virus with an envelope can acquire tissue factor, including the COVID virus, hepatitis, Zika, and dengue, to mention a few. Since infectible cells carrying tissue factor are widespread, the tissue factor axis presents a broad-spectrum anti-viral target for the first time. Thus, I am thrilled that my work will solve a critical gap in global healthcare.