title: The gamma-2-herpesvirus bovine herpesvirus 4 causes apoptotic infection in permissive cell lines.
abstract: Increasing evidence suggests that regulation of apoptosis in infected cells is associated with several viral infections. The gammaherpesvirus bovine herpesvirus 4 (BHV-4) has been shown to harbor genes with antiapoptotic potentialities. However, here we have demonstrated that productive infection of adherent, permissive cell lines by BHV-4 resulted in a cytopathic effect characterized by induction of apoptosis. This phenomenon was confirmed using different techniques to detect apoptosis and using different virus strains and cell targets. Apoptosis induced by BHV-4 was inhibited by (1) treatment with doses of heparin, which completely inhibited virus attachment and infectivity; (2) UV treatment, which completely abrogated infectivity; and (3) treatment with a dose of phosphonoacetic acid, which blocked virus replication. Virus-induced apoptosis was associated with a down-regulation of Bcl-2 expression and was reduced by Z-VAD-FMK, but not by Z-DEVD-FMK (caspase-3-specific) caspase inhibitors. Inhibition of apoptosis by Z-VAD-FMK treatment during infection did not modify virus yield. Therefore, despite the presence of antiapoptotic genes in its genoma, BHV-4 could complete its cycle of productive infection while inducing apoptosis of infected cells. This finding might have implications for the pathobiology of BHV-4 and other gammaherpesviruses in vivo.
authors.affiliation: Department of Microbiological, Genetic, and Molecular Sciences, University of Messina, Messina, Italy. mastino@med.uniroma2.it
authors.forename: M T
authors.initials: MT
authors.lastname: Sciortino
authors.forename: D
authors.initials: D
authors.lastname: Perri
authors.forename: M A
authors.initials: MA
authors.lastname: Medici
authors.forename: M
authors.initials: M
authors.lastname: Foti
authors.forename: B M
authors.initials: BM
authors.lastname: Orlandella
authors.forename: A
authors.initials: A
authors.lastname: Mastino
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D002418:Cattle Diseases / Q000821:virology; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005260:Female; D018142:Gammaherpesvirinae / Q000187:drug effects / Q000502:physiology*; D019254:Genes, bcl-2 / Q000187:drug effects; D006566:Herpesviridae Infections / Q000662:veterinary / Q000821:virology; D008414:Mastitis, Bovine / Q000821:virology; D009842:Oligopeptides / Q000494:pharmacology; D010746:Phosphonoacetic Acid / Q000494:pharmacology; D011644:Puerperal Disorders / Q000662:veterinary / Q000821:virology; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D010746:Phosphonoacetic Acid