Mechanisms of immune evasion in Epstein-Barr virus infection

Abstract

The human herpesvirus Epstein-Barr virus (EBV) is a large DNA virus that infects over 90% of the adult world population. EBV is the causative agent of infectious mononucleosis and EBV infection is associated with various malignancies. EBV establishes lifelong infections in immunocompetent hosts. To counteract the host’s immune defence, EBV acquired numerous immune evasion mechanisms. During latency of EBV, viral protein synthesis is limited or absent, making the virus-infected cells virtually invisible to the immune system. Evasion mechanisms of EBV active during primary infection as well as in reactivation are necessary for establishment of latent infection and prolonged replication. Studying viral evasion not only helps to understand EBV, but also the human immune system. Viral molecules interfering with antigen presentation by HLA I and HLA II have been identified previously, but so far, it was unclear how EBV interferes with the lipid antigen-presenting molecule CD1d. The work described in this thesis shows EBV’s mechanism to interfere with cell surface expression of CD1d. Further, a novel immune evasion molecule that obstructs antigen-presentation during the late lytic phase of EBV infection was identified and its working mechanism was unravelled. Understanding viral immune evasion mechanisms may aid in developing therapies for EBV-associated diseases.