Parvovirus Minute Virus of Mice Interacts with Sites of Cellular DNA Damage to Establish and Amplify its Lytic Infection

  1. Kinjal Majumder  Is a corresponding author
  2. Juexin Wang
  3. Maria Boftsi
  4. Matthew S Fuller
  5. Jordan E Rede
  6. Trupti Joshi  Is a corresponding author
  7. David J Pintel  Is a corresponding author
  1. University of Missouri-Columbia, United States
  2. 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.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Kinjal Majumder

    Department of Molecular Microbiology and Immunology, University of Missouri-Columbia, Columbia, United States
    For correspondence
    km3k5@health.missouri.edu
    Competing interests
    No competing interests declared.
  2. Juexin Wang

    Department of Electrical Engineering and Computer Science, University of Missouri-Columbia, Columbia, United States
    Competing interests
    No competing interests declared.
  3. Maria Boftsi

    Pathobiology Area Graduate Program, University of Missouri-Columbia, Columbia, United States
    Competing interests
    No competing interests declared.
  4. Matthew S Fuller

    Ultragenyx Pharmaceutical, Cambridge, United States
    Competing interests
    Matthew S Fuller, is employed by Ultragenyx Pharmaceutical. There are no other competing interests to declare..
  5. Jordan E Rede

    Department of Molecular Microbiology and Immunology, University of Missouri-Columbia, Columbia, United States
    Competing interests
    No competing interests declared.
  6. Trupti Joshi

    Department of Health Management and Informatics, University of Missouri-Columbia, Columbia, United States
    For correspondence
    joshitr@health.missouri.edu
    Competing interests
    No competing interests declared.
  7. David J Pintel

    Department of Molecular Microbiology and Immunology, University of Missouri-Columbia, Columbia, United States
    For correspondence
    pinteld@missouri.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9959-2848

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.

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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  1. Kinjal Majumder
  2. Juexin Wang
  3. Maria Boftsi
  4. Matthew S Fuller
  5. Jordan E Rede
  6. Trupti Joshi
  7. David J Pintel
(2018)
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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https://doi.org/10.7554/eLife.37750

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