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
Date Published2017 11
KeywordsCD36 Antigens, Cells, Cultured, DNA, DNA-Binding Proteins, Endonucleases, Erythroid Precursor Cells, Humans, Parvovirus B19, Human, Viral Nonstructural Proteins, Virus Integration

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.

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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