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Classical swine fever virus down-regulates endothelial connexin 43 gap junctions

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Abstract

Classical swine fever is a contagious disease of pigs characterized by fatal hemorrhagic fever. Classical swine fever virus (CSFV) induces the expression of pro-inflammatory and pro-coagulant factors of vascular endothelial cells and establishes a long-term infection. This study aimed to understand the effect of CSFV on endothelial connexin 43 (Cx43) expression and gap junctional intercellular coupling (GJIC). Porcine aortic endothelial cells were infected with CSFV at different multiplicity of infection for 48 h. Semi-quantitative RT-PCR, immunoconfocal microscopy, and Western blotting showed that the transcription and translation of Cx43 were reduced, and this was associated with an attenuation of GJIC. This decrease occurred in a time-dependent manner. An ERK inhibitor (PD98059), a JNK inhibitor (SP600125), and proteasome/lysosome inhibitors all significantly reversed the reduction in Cx43 protein levels without any influence on the titer of progeny virus. In addition, CSFV activated ERK and JNK in a time-dependent manner and down-regulated Cx43 promoter activity, mainly through decreased AP2 binding. This effect was primarily caused by the replication of CSFV rather than a consequence of cytokines being induced by CSFV infection of endothelial cells.

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Acknowledgments

This work is supported by the grant NSC-95-2313-B-020-005 awarded to Dr. C. Y. Wang from the National Science Council, Taiwan. Dr. Hung-I Yeh thanks the Mackay Memorial Hospital, Taiwan (MMH-E 97003), for support.

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Authors and Affiliations

  1. Department of Veterinary Medicine, National Chung Hsing University, 250 Kuo Kuang Road, Taichung, 402, Taiwan

    Hsiang-Jung Hsiao & Chi-Young Wang

  2. Graduate Institute of Biotechnology, National Pingtung University of Science and Technology, Pingtung, 912, Taiwan

    Pei-An Liu

  3. Department of Internal Medicine, Mackay Memorial Hospital, Mackay Medical College, Taipei, Taiwan

    Hung-I Yeh

Authors
  1. Hsiang-Jung Hsiao
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  2. Pei-An Liu
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  3. Hung-I Yeh
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Correspondence to Chi-Young Wang.

Additional information

H.-J. Hsiao and P. A. Liu contributed equally to this study.

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Hsiao, HJ., Liu, PA., Yeh, HI. et al. Classical swine fever virus down-regulates endothelial connexin 43 gap junctions. Arch Virol 155, 1107–1116 (2010). https://doi.org/10.1007/s00705-010-0693-1

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  • DOI: https://doi.org/10.1007/s00705-010-0693-1

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