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

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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
Issue number12
Publication statusPublished - Dec 2013



ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology


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