6533b82ffe1ef96bd1295bbb

RESEARCH PRODUCT

Parvovirus B19 nonstructural protein-induced damage of cellular DNA and resultant apoptosis.

Violetta KivovichBrian D. PooleLeona GilbertStanley J. Naides

subject

DNA RepairDNA damageViral nonstructural proteinDNA repairPoly ADP ribose polymerasevirusesBlotting WesternParvovirus B19Viral Nonstructural ProteinsCell Linechemistry.chemical_compoundsystemic lupus erythematosusParvovirus B19 HumanHumansImmunoprecipitationPolymerasebiologyfulminant liver failureDNA damage and repairapoptosisvirus diseasesGeneral MedicineTransfectionMolecular biologyProliferating cell nuclear antigenchemistrybiology.proteinDNAautoantibodyDNA DamageResearch Paper

description

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.

10.7150/ijms.8.88https://pubmed.ncbi.nlm.nih.gov/21278893