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Bovine ephemeral fever virus-induced apoptosis requires virus gene expression and activation of Fas and mitochondrial signaling pathway

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An Erratum to this article was published on 24 June 2009

Abstract

Although induction of apoptosis by bovine ephemeral fever virus (BEFV) in several cell lines has been previously demonstrated by our laboratory, less information is available on the process of BEFV-induced apoptosis in terms of cellular pathways and specific proteins involved. In order to determine the step in viral life cycle at which apoptosis of infected cells is triggered, chemical and physical agents were used to block viral infection. Treatment of BHK-21 infected cells with ammonium chloride (NH4Cl) or cells infected with UV-inactivated BEFV was seen to abrogate virus apoptosis induction, suggesting that virus uncoating and gene expression are required for the induction of apoptosis. Using soluble death receptors Fc:Fas chimera to block Fas signaling, BEFV-induced apoptosis was inhibited in cells. BEFV infection of BHK-21 cells results in the Fas-dependent activation of caspase 8 and cleavage of Bid. This initiated the dissipation of the membrane potential and the release of cytochrome c but not AIF or Smac/DIABLO from mitochondrial into cytoplasm leading to activation of caspase 9. Combined activation of the death receptor and mitochondrial pathways results in activation of the downstream effecter caspase 3 leading to cleavage of PARP. Fas-mediated BEFV-induced apoptosis could be suppressed by the overexpression of Bcl-2 or by treatment with caspase inhibitors and soluble death receptors Fc:Fas chimera. Taken together, this study provided first evidence demonstrating that BEFV-induced apoptosis requires viral gene expression and occurs through the activation of Fas and mitochondrion-mediated caspase-dependent pathways.

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Acknowledgments

This work was supported by grants awarded to Dr. Hung J. Liu by the National Science Council (NSC 95-2313-B-020-009-MY3 and NSC 97-2313-B-020-003-MY3), Taiwan.

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Authors and Affiliations

  1. Department of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan

    Chi-Hung Lin, Feng-Lang Lin, Ming-Huei Liao & Hung-Jeng Liu

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

    Chi-Hung Lin, Wen-Ling Shih & Hung-Jeng Liu

  3. Department of Pharmacy, Tajen University, Pingtung, Taiwan

    Feng-Lang Lin

  4. Tainan Hsien Livestock Disease Control Center, Tainan County, Taiwan

    Yao-Ching Hsieh

  5. Department of Plastic and Reconstructive Surgery, Chang Gung Memorial Hospital, Kaohsiung, Taiwan

    Yur-Ren Kuo

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Correspondence to Hung-Jeng Liu.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s10495-009-0377-z

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Lin, CH., Shih, WL., Lin, FL. et al. Bovine ephemeral fever virus-induced apoptosis requires virus gene expression and activation of Fas and mitochondrial signaling pathway. Apoptosis 14, 864–877 (2009). https://doi.org/10.1007/s10495-009-0371-5

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