24.05.2016
Doctoral Dissertation

27 May 2016. M.Sc. Elina Mäntylä (Faculty of Mathematics and Science, Cell and Molecular Biology)

Time:

27.5.2016 12:00 — 14:45


Location: Seminaarinmaki , Seminarium, S212
Release: 27 May 2016 Characterization of parvovirus-nucleus interactions (Mäntylä)
M.Sc. Elina Mäntylä defends her doctoral dissertation in Cell and Molecular Biology ”Import and impact - Characterization of parvovirus-nucleus interactions”. Opponent Professor José María Almendral (Centro de Biologia Molecular, Severo Ochoa, Universidad Autónoma de Madrid, Spain) and custos Docent Maija Vihinen-Ranta (University of Jyväskylä).The dissertation will be conducted in English.
Elina MäntyläM.Sc. Elina Mäntylä defends her doctoral dissertation in Cell and Molecular Biology ”Import and impact - Characterization of parvovirus-nucleus interactions”. Opponent Professor José María Almendral (Centro de Biologia Molecular, Severo Ochoa, Universidad Autónoma de Madrid, Spain) and custos Docent Maija Vihinen-Ranta (University of Jyväskylä). The dissertation will be conducted in English. 

Parvoviruses (PVs) interact with the host nucleus throughout their life cycle. During nuclear import, the nuclear envelope (NE) acts as a selective barrier limiting access to the nucleus. Inside the nucleus, the expression of viral genes has to be initiated while subjected to recognition by the host. Nuclear functions are modified to benefit viral replication, assembly, maturation and egress. However, the related mechanisms are not well known. PV´s natural oncotropism and oncolytic properties are applicable to virotherapy. Novel information on the mechanisms regulating nuclear import and viral gene expression allows for the development of parvovirus-based tools. The aims of this thesis were to characterize the nuclear import of PV, to analyze the chromatinization of the viral genome, and to elucidate the effects of the infection on the structural organization of the nucleus. Confocal microscopy with fluorescence correlation spectroscopy analyses, in situ hybridization, atomic force microscopy, biochemical assays and chromatin immunoprecipitation combined with high-throughput sequencing were used to shed light on these processes in a canine parvovirus (CPV) infection. Firstly, we found that the nuclear tethering of CPV is an active process mediated by importin β. At the NE, CPV capsids were transported into the nucleoplasm across the nuclear pore complex (NPC). Secondly, in the nucleus the CPV genome was chromatinized and the acetylation of histones (H3K27ac) at the viral promoter areas was required for the infection to proceed. Finally, a CPV infection leads to the apical enrichment of NPCs and lamin B1 with a concomitant structural modification of Nup 153. As an outcome, this thesis unravels the previously unknown dynamics of the nuclear import of PV. It describes the chromatinization of the viral genome and demonstrates the importance of its epigenetic regulation. This thesis provides insight into how PV reorganizes the nuclear architecture.

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Elina Mäntylä

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elina.h.mantyla@jyu.fi