Parvovirus minute virus of mice interacts with sites of cellular DNA damage to establish and amplify its lytic infection

• DOI: 10.7554/elife.37750
• Publication Date: 2018-07-20T12:00:23Z
• Authors: Kinjal Majumder; Juexin Wang; Maria Boftsi; Matthew S Fuller; Jordan E Rede; Trupti Joshi; David J Pintel
• Keywords: Male; 0301 basic medicine; DNA Repair; QH301-705.5; Science; Genome, Viral; topologically associating domains; DNA damage response; Virus Replication; Parvovirus; Histones; Mice; 03 medical and health sciences; Animals; Biology (General); Microbiology and Infectious Disease; 0303 health sciences; Q; R; Rats; 3. Good health; Minute Virus of Mice; Medicine; chromosome conformation capture; Genetic Engineering; DNA Damage

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).