Point Mutation Disrupting PML I Self-interaction Interferes With ND10 Formation
Author: Nolan Shoukri (biological sciences), 2021 Winner 🏆
Faculty mentor: Haidong Gu
Human herpes simplex virus 1 (HSV-1) is a prevalent virus infecting over 70% of adults that has evolved to efficiently infect its host. During infection, the antiviral ND10 nuclear bodies are used as host's efforts to repress the expression of the incoming viral genome. To counteract, HSV-1 deploys its immediate-early protein, ICP0, which colocalizes to the ND10 nuclear bodies and uses its E3 ubiquitin ligase activity to degrade important proteins at ND10. Consequently, ND10 nuclear bodies are disrupted, and the repression imposed on viral DNA is released. Promyelocytic Leukemia (PML) protein is the important structure and functional component of the cellular ND10 nuclear bodies. PML has seven isoforms that share the same N-terminus and differ only in their C-termini. The RBCC domain located in the PML N- terminus triggers PML oligomerization, which helps to build the framework of ND10. Our lab has been investigating viral and cellular elements that regulate the PML degradation triggered by ICP0. Here we report that an L73E mutation within the RBCC domain of PML I disrupts its self-interaction to the endogenous PML isoforms. Confocal microscopy assay showed that PML I containing L73E mutation fails to aggregate at ND10 nuclear bodies, but it has the ability to decrease the number of endogenous ND10 nuclear bodies. These results suggest that PML L73E mutant can dynamically interact with endogenous ND10 components and affect the ND10 restrictive ability on HSV-1 infection.
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Nolan Shoukri: Point Mutation Disrupting PML I Self-interaction Interferes With ND10 Formation