نبذة مختصرة : Various types of DNA viruses are known to elicit the formation of a large nuclear viral replication compartment and marginalization of the cell chromatin. We used three-dimensional soft x-ray tomography, confocal and electron microscopy, combined with numerical modelling of capsid diffusion to analyse the molecular organization of chromatin in herpes simplex virus 1 infection and its effect on the transport of progeny viral capsids to the nuclear envelope. Our data showed that the formation of the viral replication compartment at late infection resulted in the enrichment of heterochromatin in the nuclear periphery accompanied by the compaction of chromatin. Random walk modelling of herpes simplex virus 1-sized particles in a three-dimensional soft x-ray tomography reconstruction of an infected cell nucleus demonstrated that the peripheral, compacted chromatin restricts viral capsid diffusion, but due to interchromatin channels capsids are able to reach the nuclear envelope, the site of their nuclear egress. ; Peer reviewed
Relation: We thank the staff of Advanced Light Source (Lawrence Berkeley National Laboratory, Berkeley, CA) for providing a safe, reliable source of photons used for imaging the cells in the present study. The SXT research was conducted at the National Center for X-ray Tomography (NCXT), and first-class experimental support by Rosanne Boudreau is gratefully acknowledged. We thank Liisa Lund, Arja Strandell, Mervi Lindman and Mervi Laanti for technical assistance, and Electron Microscopy Unit of the Institute of Biotechnology, University of Helsinki, for EM sample preparation. We are grateful to Klaus Hedman for his comments on the manuscript. The project was financed by the Jane and Aatos Erkko Foundation (JT, MVR), the National Institute of General Medical Sciences of the National Institute of Health, under the award number P41 GM103445, and the US Department of Energy, Biological and Environmental Research (DE-AC02-05CH11231, CAL) and the Academy of Finland, under the award numbers 138388 (MVR) and 259725 (VH). We acknowledge the financial support from the European Community's Seventh Framework programme NMP.2013.1.4-1 under Grant Agreement no. 604005 (KM).; Aho , V , Myllys , M , Ruokolainen , V , Hakanen , S , Mantyla , E , Virtanen , J , Hukkanen , V , Kuhn , T , Timonen , J , Mattila , K , Larabell , C A & Vihinen-Ranta , M 2017 , ' Chromatin organization regulates viral egress dynamics ' , Scientific Reports , vol. 7 , 3692 . https://doi.org/10.1038/s41598-017-03630-y; http://hdl.handle.net/10138/232739; c44c81fb-5142-4cf6-b9d3-fe0cce8a8a7b; 85020932771; 000403413700054
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