title: Parvovirus B19 nonstructural protein-induced damage of cellular DNA and resultant apoptosis.
abstract: Parvovirus B19 is a widespread virus with diverse clinical presentations. The viral nonstructural protein, NS1, binds to and cleaves the viral genome, and induces apoptosis when transfected into nonpermissive cells, such as hepatocytes. We hypothesized that the cytotoxicity of NS1 in such cells results from chromosomal DNA damage caused by the DNA-nicking and DNA-attaching activities of NS1. Upon testing this hypothesis, we found that NS1 covalently binds to cellular DNA and is modified by PARP, an enzyme involved in repairing single-stranded DNA nicks. We furthermore discovered that the DNA nick repair pathway initiated by poly(ADPribose)polymerase and the DNA repair pathways initiated by ATM/ATR are necessary for efficient apoptosis resulting from NS1 expression.
authors.affiliation: Huck Institute for Life Sciences, Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center, Hershey, PA, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Poole
authors.forename: Violetta
authors.initials: V
authors.lastname: Kivovich
authors.forename: Leona
authors.initials: L
authors.lastname: Gilbert
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Naides
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D047468:Immunoprecipitation; D016732:Parvovirus B19, Human / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: C106202:NS1 protein, parvovirus; D017361:Viral Nonstructural Proteins