Date of Award
Dr. Susmit Suvas
About 90% of human beings around the world are seropositive for the Herpes Simplex Virus – 1 (HSV – 1). However, a majority of these individuals do not experience any symptoms as HSV – 1 remains in its unique latent phase most of the time. HSV – 1 can become activated if a stress is present. If this occurs, then the virus can travel to the eyes and cause inflammation. If the inflammation is not controlled within the cornea, then herpes stromal keratitis (HSK) can develop. HSV, and in turn HSK, is the leading cause of infectious blindness in the world.
CD8 T-Cells help to control HSV – 1, however, the role of its main effector protein, Granzyme B (GzmB), is not well known during the clinical phase of ocular HSV – 1 infection (i.e. post viral clearance). GzmB initiates Caspase-3 mediated apoptosis. In this project, we studied the role of GzmB in the pathogenesis of ocular HSV – 1 infection. We conducted immunofluorescence and flow cytometry experiments. Our results confirmed that CD8 T-Cells infiltrate the corneal epithelium, during the clinical phase of ocular HSV – 1 infection, and cause apoptosis through GzmB exocytosis. We also organized two experiments to determine the impact of GzmB inhibition, during the pre-clinical and clinical phase of ocular HSV – 1 infection. To inhibit GzmB, SerpinA3N, a serine protease inhibitor, was administered through subconjunctival injections. Our results provide evidence to the fact that Granzyme B activity plays a role in HSK development, and its inhibition has therapeutic potential in ocular HSV – 1 infection.
Nagda, Maharshi Sanjay, "The Role of Granzyme B in the Pathogenesis of Ocular HSV – 1 Infection" (2018). Honors College Theses. 43.