Chang_PNAS_forUIC-INDIGO_061311.pdf (930.59 kB)
Herpesviral Replication Compartments Move and Coalesce at Nuclear Speckles to Enhance Export of Viral Late mRNA
journal contributionposted on 2012-03-09, 00:00 authored by Lynn Chang, William J. Godinez, Il-Han Kim, Marco Tektonidis, Primal de Lanerolle, Roland Eils, Karl Rohr, David M. Knipe
The role of the intranuclear movement of chromatin in gene expression is not well understood. Herpes simplex virus forms replication compartments (RCs) in infected cell nuclei as sites of viral DNA replication and late gene transcription. These structures develop from small compartments that grow in size, move and coalesce. Quantitative analysis of RC trajectories, derived from 4D images, show that most RCs move by directed motion. Directed movement is impaired in the presence of actin and myosin inhibitors as well as a transcription inhibitor. In addition, RCs coalesce at and reorganize nuclear speckles. Lastly, distinct effects of actin and myosin inhibitors on viral gene expression suggest that RC movement is not required for transcription but rather, movement results in the bridging of transcriptionally active RCs with nuclear speckles to form structures that enhance export of viral late mRNAs.
We thank the New England Regional Center for Excellence for Biodefense 26 and Emerging Infectious Diseases (National Institutes of Health Grant AI057159) imaging facility at the Immune Disease Institute for use of the spinning disk confocal microscope. Funding for this work was provided by NIH grant AI63106 to DMK and RO1GM080587 to PdL. Support for the project VIROQUANT (0313923) by the German Federal Ministry of Education and Research (BMBF) (FORSYS) is also acknowledged.
Publisher Statement© National Academy of Sciences, Proceedings of the National Academy of Sciences of the United States of America. Post print version of article may differ from published version. The definitive version is available through the National Academy of Sciences at DOI: 10.1073/pnas.1103411108.
PublisherNational Academy of Sciences