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Modulation of apoptosis by caprine herpesvirus 1 infection in a neuronal cell line

Authors

  • Serena Montagnaro,

    1. Department of Veterinary Medicine and Animal Productions, University of Naples “Federico II”, Naples, Italy
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  • Roberto Ciarcia,

    1. Department of Veterinary Medicine and Animal Productions, University of Naples “Federico II”, Naples, Italy
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  • Claudio De Martinis,

    1. Department of Veterinary Medicine and Animal Productions, University of Naples “Federico II”, Naples, Italy
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  • Carmen Pacilio,

    1. Department of Veterinary Medicine and Animal Productions, University of Naples “Federico II”, Naples, Italy
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  • Simona Sasso,

    1. Department of Veterinary Medicine and Animal Productions, University of Naples “Federico II”, Naples, Italy
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  • Maria Valeria Puzio,

    1. Department of Veterinary Medicine and Animal Productions, University of Naples “Federico II”, Naples, Italy
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  • Morena De Angelis,

    1. Department of Veterinary Medicine and Animal Productions, University of Naples “Federico II”, Naples, Italy
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  • Ugo Pagnini,

    Corresponding author
    1. Department of Veterinary Medicine and Animal Productions, University of Naples “Federico II”, Naples, Italy
    • Correspondence to: Prof. Ugo Pagnini, University of Naples “Federico II”, Department of Veterinary Medicine and Animal Productions, University of Naples “Federico II”, Via Delpino 1, 80137 Napoli, Italy.

      E-mail: upagnini@unina.it

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  • Silvia Boffo,

    1. Sbarro Institute for Cancer Research and Molecular Medicine, Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania
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  • Ivanna Kenez,

    1. Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
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  • Giuseppe Iovane,

    1. Department of Veterinary Medicine and Animal Productions, University of Naples “Federico II”, Naples, Italy
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  • Antonio Giordano

    1. Sbarro Institute for Cancer Research and Molecular Medicine, Center of Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania
    2. Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy
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ABSTRACT

Caprine herpesvirus type 1 (CpHV-1), like other members of the alpha subfamily of herpesviruses, establishes latent infections in trigeminal ganglion neurons. Our groups previously demonstrated that CpHV-1 induces apoptosis in goat peripheral blood mononuclear cells and in an epithelial bovine cell line, but the ability of CpHV-1 to induce apoptosis in neuronal cells remains unexplored. In this report, the susceptibility of Neuro 2A cells to infection by CpHV-1 was examined. Following infection of cultured cells with CpHV-1, expression of cell death genes was evaluated using real-time PCR and Western blot assays. Analysis of virus-infected cells revealed activation of caspase-8, a marker for the extrinsic pathway of apoptosis, and caspase-9, a marker for the intrinsic pathway of apoptosis at 12 and 24 h post-infection. Significant increase in the levels of cleaved caspase-3 was also observed at the acme of cytopathic effect at 24 h post-infection. In particular, at 3 and 6 h post-infection, several proapototic genes were under-expressed. At 12 h post-infection several proapototic genes such as caspases, TNF, Cd70, and Traf1 were over expressed while Bcl2a1a, Fadd, and TNF genes were underexpressed. In conclusion, the simultaneous activation of caspase-8 and caspase-9 suggests that CpHV-1 can trigger the death-receptor pathway and the mitochondrial pathway separately and in parallel. Our findings are significant because this is the first published study showing the effect of CpHV-1 infection in neuronal cells in terms of gene expression and apoptosis modulation. J. Cell. Biochem. 114: 2809–2822, 2013. © 2013 Wiley Periodicals, Inc.

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