Possible TAP inhibitors in HHV-6 and HHV-7 based on known characteristics of TAP inhibitors and their evolutionary development in herpesviruses.

Abstract

Herpesviruses are well-known because of their latency and immune evasion strategies. The MHC class I antigen presentation pathway is an important target, especially MHC class I downregulation. Downregulation of MHC molecules can be accomplished in different ways. One of those ways extensively used by herpesviruses, tumors and even cowpoxvirus is to inhibit peptide loading onto the MHC class I molecules by blocking the transporter associated with antigen presentation (TAP). All subfamilies of the herpesviridae encode for different TAP inhibitors. As for the human herpesviruses, only varicella zostervirus (VZV), human herpesvirus (HHV-) 6 and HHV-7 have no known TAP inhibitors. In this thesis a list is generated with possible TAP inhibitors for the β-herpesviruses HHV-6 and HHV-7. The list is based on several characteristics shared by the known TAP inhibitors . More importantly, the evolutionary development of herpesviruses and their immune evasion proteins suggests that relatively new genes will be located near the ends of the genomes. In this study a clear picture has been drawn to show that this is true for the TAP inhibitors and that this might be a great tool to predict the location of immune evasion proteins.