Host cell-derived tissue factor as a broad-spectrum basis for viral pathology and infection

Well-balanced blood clotting is essential for health and has life-threatening impact when tipped off-balance. Many viruses are known to trigger an infected person's blood clotting system and cause a wide range of clotting-related clinical problems; from heart disease to bleeding. The processes used by the virus to cause these diseases are poorly understood. Using the oral herpes virus (HSV1) as a model virus, our lab has shown that these germs hijack clotting activators to increase infection. To understand how, the current proposal focuses on our 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 life. Many viruses are covered with a membrane, called an envelope, which is acquired from our infected cells and can therefore contain tissue factor. Why is tissue factor important? Because it is the initiator of blood clotting and it also alters the function of cells. Here we propose to expand our findings in HSV1 and extend our knowledge to HIV and dengue virus, both major global problems. We will take biochemical and animal approaches to test our ideas, which have already revealed possible strategies to treat these virus infections. In addition to these viruses, many others that burden healthcare systems world-wide have an envelope, such as influenza, Ebola, hepatitis C and Zika viruses. The five virus types we have investigated to date all have tissue factor, suggesting that any virus with an envelope can acquire tissue factor. Since cells containing tissue factor are found throughout the body and are infected by many types of virus, we anticipate that targeting tissue factor found on the surface of viruses will allow us to treat a wide-range of viral infections and fill a serious deficiency in global healthcare.