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.: Home > International Journal of Medical Sciences > 2011 > Volume 8 Number 2 > Brian D. Poole1,2, Violetta Kivovich1,3,4,5, Leona Gilbert4,5 and Stanley J. Naides1, 5,6

Parvovirus B19 Nonstructural Protein-Induced Damage of Cellular DNA and Resultant Apoptosis

Brian D. Poole1,2, Violetta Kivovich1,3,4,5, Leona Gilbert4,5 and Stanley J. Naides1, 5,6
1. Huck Institute for Life Sciences, Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center, Hershey, PA, USA 2. Current: Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, USA 3. MD/PhD Program, Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center, Hershey, PA, USA 4. Chemical Biology Division, Department of Biological and Environmental Science, University of Jyvنskylن, Jyvنskylن, Finland 5. Division of Rheumatology, Department of Medicine, Pennsylvania State University College of Medicine/Milton S. Hershey Medical Center, Hershey, PA, USA 6. Current: Quest Diagnostics Nichols Institute, San Juan Capistrano, CA, USA
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.

Keywords :
Parvovirus B19, DNA damage and repair, fulminant liver failure, apoptosis, autoantibody, systemic lupus erythematosus

Date Deposited : 04 Jul 2011 10:44

Last Modified : 04 Jul 2011 10:44

Official URL: http://www.medsci.org/

Volume 8, Number 2, - 2011 , ISSN 1449-1907

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