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Ochratoxin A promotes porcine circovirus type 2 replication in vitro and in vivo

Lookup NU author(s): Professor John Hesketh, Dr Patience Ezea

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Abstract

Ochratoxin A (OTA), a worldwide mycotoxin found in food and feeds, is a potent nephrotoxin in animals and humans. Porcine circovirus-associated disease (PCVAD), including porcine dermatitis and nephropathy syndrome, is a worldwide swine disease. To date, little is known concerning the relationship between OTA and porcine circovirus type 2 (PCV2), the primary causative agent of PCVAD. The effects of OTA on PCV2 replication and their mechanisms were investigated in vitro and in vivo. The results in vitro showed that low doses of OTA significantly increased PCV2 DNA copies and the number of infected cells: Maximum effects were observed at 0.05 mu g/ml OTA. The results in vivo showed that PCV2 replication was significantly increased in serum and tissues of pigs fed 75 mu g/kg OTA compared with the control group and pigs fed 150 mu g/kg OTA. In addition, low doses of OTA significantly depleted reduced glutathione and mRNA expression of NF-E2-related factor 2 and gamma-glutamylcysteine synthetase; increased reactive oxygen species, oxidants, and malondialdehyde; and induced p38 and ERK1/2 phosphorylation in PK15 cells. Adding N-acetyl-L-cysteine reversed the changes induced by OTA. Knockdown of p38 and ERK1/2 by their respective specific siRNAs or inhibition of p38 and ERK1/2 phosphorylation by their respective inhibitors (SB203580 and U0126) eliminated the increase in PCV2 replication induced by OTA. These data indicate that low doses of OTA promoted PCV2 replication in vitro and in vivo via the oxidative stress-mediated p38/ERK1/2 MAPK signaling pathway. This suggests that low doses of OTA are potentially harmful to animals, as they enhance virus replication, and partly explains why the morbidity and severity of PCVAD vary significantly in different pig farms. (C) 2014 Elsevier Inc. All rights reserved.


Publication metadata

Author(s): Gan F, Zhang ZQ, Hu ZH, Hesketh J, Xue HX, Chen XX, Hao S, Huang Y, Ezea PC, Parveen F, Huang KH

Publication type: Article

Publication status: Published

Journal: Free Radical Biology and Medicine

Year: 2015

Volume: 80

Pages: 33-47

Print publication date: 01/03/2015

Online publication date: 24/12/2014

Acceptance date: 15/12/2014

ISSN (print): 0891-5849

ISSN (electronic): 1873-4596

Publisher: Elsevier

URL: http://dx.doi.org/10.1016/j.freeradbiomed.2014.12.016

DOI: 10.1016/j.freeradbiomed.2014.12.016


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Funding

Funder referenceFunder name
NSFC
Priority Academic Program Development of Jiangsu Higher Education Institutions (Jiangsu, China)
Royal Society
20120097130002Research Fund for Doctoral Programs of Higher Education in China
20110097110014Research Fund for Doctoral Programs of Higher Education in China
31272627National Natural Science Foundation of China
31472253National Natural Science Foundation of China

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