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Cambridge Institute for Medical Research

AlphaFold multimer model highlighting the predicted BILF1 and MAVS interaction domain and residues.

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.