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

Serena Montagnaro, Roberto Ciarcia, Claudio De Martinis, Carmen Pacilio, Simona Sasso, Maria Valeria Puzio, Morena De Angelis, Ugo Pagnini, Silvia Boffo, Ivanna Kenez, Giuseppe Iovane, Antonio Giordano

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2809-2822
Number of pages14
JournalJournal of Cellular Biochemistry
Volume114
Issue number12
DOIs
Publication statusPublished - Dec 2013

Keywords

  • APOPTOSIS
  • CAPRINE HERPESVIRUS TYPE 1
  • GENE EXPRESSION
  • NEURONS

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

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  • Cite this

    Montagnaro, S., Ciarcia, R., De Martinis, C., Pacilio, C., Sasso, S., Puzio, M. V., De Angelis, M., Pagnini, U., Boffo, S., Kenez, I., Iovane, G., & Giordano, A. (2013). Modulation of apoptosis by caprine herpesvirus 1 infection in a neuronal cell line. Journal of Cellular Biochemistry, 114(12), 2809-2822. https://doi.org/10.1002/jcb.24628