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Cellular factors restricting mouse polyomavirus infection in host cells: Studies of PML protein isoforms
Anderová, Karolína ; Forstová, Jitka (advisor) ; Němečková, Šárka (referee)
Promyelocytic leukaemia nuclear bodies (PML NBs) are multifunctional nuclear spherical structures formed by the PML protein shell and other interaction partners that have been described to be involved in many cellular processes and immune defences. In the antiviral immune response, PML NBs and their components act as direct restriction factors as well as in the regulation of the interferon response. On the other hand, viruses have developed antagonistic mechanisms to resist this inhibition. This work deals with the role of PML NBs in infection with model Murine polyomavirus (MPyV) and focuses on the study of PML protein isoforms. The first aim of the work was to analyse the formation of human (hPML) and mouse (mPML) NBs in a mouse embryonic fibroblast (MEF) model. Subsequently, the localization of hPML and mPML NBs during infection was determined. Close localization with viral replication centres was observed for both PML species. In the next step, the effect of infection or interferon α (IFNα) on mPML protein expression was tested. Infection and treatment with IFNα led to an increase in mPML expression at the level of both gene transcription and protein synthesis. At the same time, the data indicated the largest increase in transcription of the mPML3 isoform. The work also addressed the potential...
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Intracellular restriction factors of small DNA viruses
Anderová, Karolína ; Forstová, Jitka (advisor) ; Pokrývková, Barbora (referee)
The theme of this work is to summarize knowledge about protein restriction factors, which function in cells infected by small DNA viruses of families Hepadnaviridae, Parvoviridae, Polyomaviridae and Papillomaviridae. Both restriction factors induced by interferon and restriction factors of intrinsic immunity which are constitutively produced in cells are included in this work. At the same time, mechanisms by which viruses overcome the inhibition effects of restriction factors are mentioned. Restriction factors suppressing Hepatitis B virus infection like components of PML nuclear bodies and proteins Smc5/6, SAMHD1, APOBEC, TRIM, ZAP and Tetherin are described. For the representatives of Parvoviridae family, deaminases APOBEC and PML protein were identified as restriction factors. For the infection by polyomaviruses, restriction factors FAM111A and SRSF1 were described. Restriction by PML nuclear bodies and its component Sp100 and proteins APOBEC, IFI16 and IFIT1 is discussed for the Papillomaviridae family. Keywords: small DNA viruses, intracellular DNA sensing, restriction factors, viral antagonistic mechanisms
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