Quantitative Microscopy Reveals Stepwise Alteration of Chromatin Structure during Herpesvirus Infection
Aho, V., Mäntylä, E., Ekman, A., Hakanen, S., Mattola, S., Chen, J.-H., Weinhardt, V., Ruokolainen, V., Sodeik, B., Larabell, C., & Vihinen-Ranta, M. (2019). Quantitative Microscopy Reveals Stepwise Alteration of Chromatin Structure during Herpesvirus Infection. Viruses, 11(10), Article 935. https://doi.org/10.3390/v11100935
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VirusesAuthors
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2019Copyright
© Authors, 2019
During lytic herpes simplex virus 1 (HSV-1) infection, the expansion of the viral replication compartments leads to an enrichment of the host chromatin in the peripheral nucleoplasm. We have shown previously that HSV-1 infection induces the formation of channels through the compacted peripheral chromatin. Here, we used three-dimensional confocal and expansion microscopy, soft X-ray tomography, electron microscopy, and random walk simulations to analyze the kinetics of host chromatin redistribution and capsid localization relative to their egress site at the nuclear envelope. Our data demonstrated a gradual increase in chromatin marginalization, and the kinetics of chromatin smoothening around the viral replication compartments correlated with their expansion. We also observed a gradual transfer of capsids to the nuclear envelope. Later in the infection, random walk modeling indicated a gradually faster transport of capsids to the nuclear envelope that correlated with an increase in the interchromatin channels in the nuclear periphery. Our study reveals a stepwise and time-dependent mechanism of herpesvirus nuclear egress, in which progeny viral capsids approach the egress sites at the nuclear envelope via interchromatin spaces.
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Jane and Aatos Erkko FoundationFunding program(s)
FoundationAdditional information about funding
This research was funded by the Jane and Aatos Erkko Foundation (M.V-R.), 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, C.A.L.), and the German Research Foundation (CRC 900, project C2, B.S.)License
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