Parvovirus Induced Alterations in Nuclear Architecture and Dynamics

The nucleus of interphase eukaryotic cell is a highly compartmentalized structure containing the three-dimensional network of chromatin and numerous proteinaceous subcompartments. DNA viruses induce profound changes in the intranuclear structures of their host cells. We are applying a combination of confocal imaging including photobleaching microscopy and computational methods to analyze the modifications of nuclear architecture and dynamics in parvovirus infected cells. Upon canine parvovirus infection, expansion of the viral replication compartment is accompanied by chromatin marginalization to the vicinity of the nuclear membrane. Dextran microinjection and fluorescence recovery after photobleaching (FRAP) studies revealed the homogeneity of this compartment. Markedly, in spite of increase in viral DNA content of the nucleus, a significant increase in the protein mobility was observed in infected compared to non-infected cells. Moreover, analyzis of the dynamics of photoactivable capsid protein demonstrated rapid intranuclear dynamics of viral capsids. Finally, quantitative FRAP and cellular modelling were used to determine the duration of viral genome replication. Altogether, our findings indicate that parvoviruses modify the nuclear structure and dynamics extensively. Intranuclear crowding of viral components leads to enlargement of the interchromosomal domain and to chromatin marginalization via depletion attraction. In conclusion, parvoviruses provide a useful model system for understanding the mechanisms of virus-induced intranuclear modifications

Distribution and dynamics of transcription-associated proteins during parvovirus infection.

Canine parvovirus (CPV) infection leads to reorganization of nuclear proteinaceous subcompartments. Our studies showed that virus infection causes a time-dependent increase in the amount of viral nonstructural protein NS1 mRNA. Fluorescence recovery after photobleaching showed that the recovery kinetics of nuclear transcription-associated proteins, TATA binding protein (TBP), transcription factor IIB (TFIIB), and poly(A) binding protein nuclear 1 (PABPN1) were different in infected and noninfected cells, pointing to virus-induced alterations in binding dynamics of these proteins.peerReviewe

Matching voters to parties: voting advice applications and models of party choice

Online voting advice applications (VAAs) have become very popular and may significantly influence voting behaviour. It is therefore important to ask which model of party choice VAAs follow. We establish that VAAs see party choice largely as proximity-based issue congruence, with some elements of the directional and salience models. We then assess how well VAAs follow the proximity model by comparing policy positions extracted from 13 VAAs in seven European countries with established policy measures from expert surveys and party manifestos. Party positions extracted from VAAs show strong convergent validity with left-right and economic positions, but compare less favourably with immigration and environment measures. The voting advice given to users is also inherently limited: VAAs mostly disregard accountability, salience, competence and non-policy factors; they treat policy positions and not outcomes as paramount; and they can be subject to strategic manipulation by political parties. As recommended by their designers, voters should treat these applications as tools and guides rather than as stringent recommendations