Manipulation of the Human Lymphocyte Antigen Class II Processing Pathway by Herpes Simplex Virus Encoded Glycoprotein B

• Applicant: Professor Dr. Norbert Koch
• Subject Area: Immunology
• Term: from 2010 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 183381352

Infection with Herpes Simplex virus type 1 (HSV-1) elicits an effective immune response, but numerous viral evasion strategies prevent complete elimination of the virus. Molecular targets for immune evasion upon HSV-1 infection are HLA-DR molecules, which are high jacked by the HSV-1 encoded glycoprotein B (gB). This viral protein impairs the physiological role of HLA-DR to present viral peptides to the immune system. gB directs the MHC class II processing pathway from antigen presentation to disposal of HLA-DR molecules through exosomal release. The physiological exosomal release is strongly elevated by expression of gB. In this project the role of viral gB on intracellular sorting and on exosomal secretion will be investigated. Aim of our project is to explain how gB interferes with the biogenesis of endosomes and the generation of exosomes. It is possible that secreted gB- exosomes modulate immune responses. We want to explore the impact of gB expressing exosomes on immune reactions and determine whether exosomes play a role for communication of infected with immune cells. Our results could provide a novel mechanism how viral intrusion manipulates cellular immune responses.

• DFG Programme: Research Grants