ATRX promotes maintenance of herpes simplex virus heterochromatin during chromatin stress
The mechanisms by which mammalian cells recognize and epigenetically restrict viral DNA are not well defined. We used herpes simplex virus with bioorthogonally labeled genomes to detect host factors recruited to viral DNA shortly after its nuclear entry and found that the cellular IFI16, PML, and ATRX proteins colocalized with viral DNA by 15 min post infection. HSV-1 infection of ATRX-depleted fibroblasts resulted in elevated viral mRNA and accelerated viral DNA accumulation. Despite the early association of ATRX with vDNA, we found that initial viral heterochromatin formation is ATRX-independent. However, viral heterochromatin stability required ATRX from 4-8 h post infection. Inhibition of transcription blocked viral chromatin loss in ATRX-knockout cells; thus, ATRX is uniquely required for heterochromatin maintenance during chromatin stress. These results argue that the initial formation and the subsequent maintenance of viral heterochromatin are separable mechanisms, a concept that likely extrapolates to host cell chromatin and viral latency.
All data generated or analyzed during this study are included in the manuscript and supporting files. MATLAB based software developed to generate image analysis data is available for use: doi:10.5061/dryad.95fs76f
Data from: ATRX promotes maintenance of herpes simplex virus heterochromatin during chromatin stressDryad Digital Repository, doi:10.5061/dryad.95fs76f.
Article and author information
National Institutes of Health (AI106934)
- David M Knipe
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Stephen P Goff, Howard Hughes Medical Institute, Columbia University, United States
- Received: July 19, 2018
- Accepted: November 20, 2018
- Accepted Manuscript published: November 22, 2018 (version 1)
- Version of Record published: December 27, 2018 (version 2)
© 2018, Cabral et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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