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

被引：25

作者：

Poole, Brian D. ^{[1
]}

Kivovich, Violetta ^{[1
,2
,3
,4
]}

Gilbert, Leona ^{[3
,4
]}

Naides, Stanley J. ^{[1
,4
]}

机构：

[1] Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Huck Inst Life Sci, Hershey, PA 17033 USA

[2] Penn State Univ, Milton S Hershey Med Ctr, Coll Med, MD PhD Program, Hershey, PA 17033 USA

[3] Univ Jyvaskyla, Chem Biol Div, Dept Biol & Environm Sci, Jyvaskyla, Finland

[4] Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Div Rheumatol,Dept Med, Hershey, PA 17033 USA

来源：

INTERNATIONAL JOURNAL OF MEDICAL SCIENCES | 2011年 / 8卷 / 02期

关键词：

Parvovirus B19; DNA damage and repair; fulminant liver failure; apoptosis; autoantibody; systemic lupus erythematosus; ACUTE LIVER-FAILURE; POLYOMAVIRUS T-ANTIGEN; MINUTE VIRUS; APLASTIC-ANEMIA; NS1; PROTEIN; TRANSCRIPTION FACTORS; REPLICATION BODIES; GENOME INTEGRITY; MOLECULAR-BASIS; NS-1;

D O I：

10.7150/ijms.8.88

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：88 / 96

页数：9

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