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Parvovirus B19 integration into human CD36+ erythroid progenitor cells.

TitleParvovirus B19 integration into human CD36+ erythroid progenitor cells.
Publication TypeJournal Article
Year of Publication2017
AuthorsJanovitz T, Wong S, Young NS, Oliveira T, Falck-Pedersen E
JournalVirology
Volume511
Pagination40-48
Date Published2017 11
ISSN1096-0341
KeywordsCD36 Antigens, Cells, Cultured, DNA, DNA-Binding Proteins, Endonucleases, Erythroid Precursor Cells, Humans, Parvovirus B19, Human, Viral Nonstructural Proteins, Virus Integration
Abstract

The pathogenic autonomous human parvovirus B19 (B19V) productively infects erythroid progenitor cells (EPCs). Functional similarities between B19V nonstructural protein (NS1), a DNA binding endonuclease, and the Rep proteins of Adeno-Associated Virus (AAV) led us to hypothesize that NS1 may facilitate targeted nicking of the human genome and B19 vDNA integration. We adapted an integration capture sequencing protocol (IC-Seq) to screen B19V infected human CD36+ EPCs for viral integrants, and discovered 40,000 unique B19V integration events distributed throughout the human genome. Computational analysis of integration patterns revealed strong correlations with gene intronic regions, H3K9me3 sites, and the identification of 41 base pair consensus sequence with an octanucleotide core motif. The octanucleotide core has homology to a single region of B19V, adjacent to the P6 promoter TATA box. We present the first direct evidence that B19V infection of erythroid progenitor cells disrupts the human genome and facilitates viral DNA integration.

DOI10.1016/j.virol.2017.08.011
Alternate JournalVirology
PubMed ID28806616
PubMed Central IDPMC5623651
Grant ListR01 AI094050 / AI / NIAID NIH HHS / United States
T32 GM007739 / GM / NIGMS NIH HHS / United States

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