The Gamma-2-herpesvirus bovine herpesvirus 4 causes apoptotic infection inpermissive cell lines

Increasing evidence suggests that regulation of apoptosis in infected cells is associated with several viral infections. The gammaherpesvirus bovine h erpesvirus 4 (BHV-4) has been shown to harbor genes with antiapoptotic pote ntialities. However, here we have demonstrated that productive infection of adherent, permissive cell lines by BHV-4 resulted in a cytopathic effect c haracterized 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) treatmen t with doses of heparin, which completely inhibited virus attachment and in fectivity; (2) UV treatment, which completely abrogated infectivity; and (3 ) treatment with a dose of phosphonoacetic acid, which blocked virus replic ation. 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 treatm ent during infection did not modify virus yield. Therefore, despite the pre sence of antiapoptotic genes in its genoma, BHV-4 could complete its cycle of productive infection while inducing apoptosis of infected cells. This fi nding might have implications for the pathobiology of BHV-4 and other gamma herpesviruses in vivo, (C) 2000 Academic Press.