Two types of autophagy in pathogenesis and antigen presentation of Herpes Simplex Virus type 1

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Herpes simplex virus type 1 (HSV1) is endemic in about 70 - 80% of the world's population, causes diseases varying in severity from cold sores to life threatening encephalitis, and is implicated in the progression of Alzheimers disease. Furthermore, a HSV1 infection of the eyes is the most common cause of blindness in Africa, and widespread in North America and Europe. How this virus is controlled by the immune system is still little understood. I propose to analyse how specific antiviral immune cells (killer cells) recognise HSV1 infected cells. In particular, I want to find out how a cellular process termed autophagy (self-eating) contributes to this. Autophagy is involved in the recycling of nutrients, the clearance of intracellular pathogens and adaptive antiviral immunity. A contribution of this pathway to immune recognition by killer cells has recently been described by my host laboratory. In addition to cytosolic autophagy, they observed a novel nuclear autophagy pathway. The components and molecular mechanism of this alternative autophagy pathway are so far unknown. A better understanding of the mechanism of this novel autophagy pathway and the contribution of both types of autophagy to antiviral immunity might lead to the development of novel drugs against this virus and related herpesviruses. Furthermore, it might allow a manipulation of the immune system of patients, either by enhancing the immune response for faster recovery from severe infections, or by downregulating the immune response in patients that are receiving a herpesvirus-infected organ transplant.