Interakce jaderných tělísek PML a myšího polyomaviru: vizualizace replikačních center a role izoforem mPML ve vrozené imunitě

Mališová, Pavla

The mammalian immune response to viral infection relies on a coordinated effort between innate signalling, driven by the type I interferon (IFN) response, and intrinsic immunity, mediated by constitutive restriction factors. An important component at this interface is the promyelocytic leukaemia (PML) protein, the structural scaffold of PML nuclear bodies (PML NBs). PML NBs and PML protein actively participate in the cellular antiviral response. Among the human PML variants, isoforms hPMLII and hPMLIV have been shown to positively regulate the type I IFN pathway. While PML NBs are established mediators of antiviral defence, their interaction with the Polyomaviridae family represents a biological paradox: despite the restrictive potential of these structures, polyomaviruses actively localise their replication and assembly in close proximity to them. Using murine polyomavirus (MPyV) as a model system, this thesis explores the functional and spatial role of murine PML and PML NBs during viral infection. To investigate the spatial dynamics of this interplay, a CRISPR/dCas9 visualisation system was adapted to specifically target and track MPyV DNA within viral replication centres. The targeting capability and functionality of this system were successfully validated in both fixed and living cells....

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