title: Modulation of apoptosis by caprine herpesvirus 1 infection in a neuronal cell line.
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.
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples "Federico II", Via Delpino no. 1, 80137, Naples, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Montagnaro
authors.forename: Roberto
authors.initials: R
authors.lastname: Ciarcia
authors.forename: Claudio
authors.initials: C
authors.lastname: De Martinis
authors.forename: Carmen
authors.initials: C
authors.lastname: Pacilio
authors.forename: Simona
authors.initials: S
authors.lastname: Sasso
authors.forename: Maria Valeria
authors.initials: MV
authors.lastname: Puzio
authors.forename: Morena
authors.initials: M
authors.lastname: De Angelis
authors.forename: Ugo
authors.initials: U
authors.lastname: Pagnini
authors.forename: Silvia
authors.initials: S
authors.lastname: Boffo
authors.forename: Ivanna
authors.initials: I
authors.lastname: Kenez
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Iovane
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D053148:Caspase 3 / Q000096:biosynthesis; D053181:Caspase 8 / Q000096:biosynthesis; D053453:Caspase 9 / Q000096:biosynthesis; D002417:Cattle; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D005786:Gene Expression Regulation; D006566:Herpesviridae Infections / Q000235:genetics* / Q000473:pathology / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D018140:Varicellovirus / Q000235:genetics* / Q000472:pathogenicity
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9
keywords: APOPTOSIS; CAPRINE HERPESVIRUS TYPE 1; GENE EXPRESSION; NEURONS