Parvovirus Minute Virus of Mice Interacts with Sites of Cellular DNA Damage to Establish and Amplify its Lytic Infection
- University of Missouri-Columbia, United States
- Ultragenyx Pharmaceutical, United States
Abstract
We have developed a generally adaptable, novel high-throughput Viral Chromosome Conformation Capture assay (V3C-seq) for use in trans that allows genome-wide identification of the direct interactions of a lytic virus genome with distinct regions of the cellular chromosome. Upon infection, we found that the parvovirus Minute Virus of Mice (MVM) genome initially associated with sites of cellular DNA damage that in mock-infected cells also exhibited DNA damage as cells progressed through S-phase. As infection proceeded, new DNA damage sites were induced, and virus subsequently also associated with these. Sites of association identified biochemically were confirmed microscopically and MVM could be targeted specifically to artificially induced sites of DNA damage. Thus, MVM established replication at cellular DNA damage sites, which provide replication and expression machinery, and as cellular DNA damage accrued, virus spread additionally to newly damaged sites to amplify infection. MVM-associated sites overlap significantly with previously identified topologically-associated domains (TADs).
Data availability
Sequencing data have been deposited in GEO under accession codes GSE81295 and GSE112957. Reviewers may use the following private token to access the data while it is in private status is: srufuwisdhiplgf.
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Parvovirus Minute Virus of Mice Localizes to Sites of Cellular DNA Damage to Establish and Amplify its Lytic InfectionPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE112957).
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Article and author information
Author details
Funding
National Institute of Allergy and Infectious Diseases (AI046458)
- David J Pintel
National Institute of Allergy and Infectious Diseases (AI131468)
- Kinjal Majumder
National Institute of Allergy and Infectious Diseases (AI116595)
- David J Pintel
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- David M Knipe, Harvard Medical School, United States
Version history
- Received: April 21, 2018
- Accepted: July 19, 2018
- Accepted Manuscript published: July 20, 2018 (version 1)
- Version of Record published: August 16, 2018 (version 2)
Copyright
© 2018, Majumder 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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Parvovirus Minute Virus of Mice Interacts with Sites of Cellular DNA Damage to Establish and Amplify its Lytic Infection
eLife 7:e37750.
https://doi.org/10.7554/eLife.37750
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