Prof Mike Weekes’s lab works to understand how viruses including human cytomegalovirus (HCMV) and Epstein-Barr virus (EBV) interact with and evade host cell antiviral proteins. EBV is associated with around 2% of human cancers, including Hodgkin lymphoma, and is a trigger for multiple sclerosis. Much is unknown about how EBV remodels host cells and dismantles their key antiviral defences, and the function of many EBV-encoded proteins is incompletely understood.
In collaboration with colleagues from Harvard Medical School and Brigham and Women’s Hospital, a new Weekes lab paper in Molecular Cell describes creation of a proteomic map of EBV-host and EBV-EBV interactions in B cells undergoing EBV replication. The results revealed a wide array of virus/ host interactions and provide a viral protein interaction network resource. Using the map, an unexpected mechanism by which EBV inhibits NLRP3 inflammasome activation was revealed. The EBV-encoded G-protein coupled receptor BILF1 provides a means to selectively degrade mitochondrial membrane cargo, thus identifying the BILF1 receptor as a novel therapeutic target. Additionally, cross-comparison with HCMV and Kaposi sarcoma-associated herpesvirus identified common host protein nodes widely targeted by human herpesviruses.