Project 467146

Epstein-Barr virus (EBV) is a common human herpesvirus that spreads mainly through saliva, often leading to mononucleosis upon initial infection before setting up a lifetime infection. Lifetime infections involve alternation between latent and lytic modes of infection and can lead to several types of cancer. Recently our lab found that the cellular Sal-like protein 4 (SALL4) was highly expressed during the lytic cycle of EBV infection, and it was also found to be highly modified by Small Ubiquitin-like Modifier (SUMO) proteins. Adding SUMO to certain proteins can change their function in cells, including the proteins they bind and the processes they regulate. My goal is to determine why SUMO-modified SALL4 is important for EBV lytic infection and whether it has a role in the antiviral response. I will examine how SALL4 levels are affected in EBV infection of multiple cell types including B cell lymphomas, gastric carcinoma, and nasopharyngeal carcinoma, all of which can be induced by EBV infection. I will also determine the cellular and viral proteins that interact with SALL4 in the context of EBV infection in order to identify the cellular pathways that SALL4 is controlling and the EBV proteins that might target SALL4 to interfere with its functions. These studies will also be performed with SALL4 mutants that cannot be SUMO-modified in order to determine how this modification affects the functions of SALL4. Finally, I will knock out SALL4 in EBV-infected cells and determine how this affects EBV infection. Together these experiments will help us to understand the role of SALL4 in EBV infection and whether it is part of a novel antiviral response.