Infected cell protein 0 encoded by bovine herpesvirus 1 can activate caspase 3 when overexpressed in transfected cells.
Infection of cattle or bovine cells with bovine herpesvirus 1 (BHV-1) leads to increased apoptosis. Previous studies indicated that BHV-1 infected cell protein 0 (bICP0), the major transcriptional regulatory protein of BHV-1, is toxic in transiently transfected cells. Point mutations within the zinc RING finger of bICP0 reduced toxicity and eliminated the ability of bICP0 to activate viral gene expression. In mouse neuroblastoma cells (neuro-2A) and bovine turbinate cells, bICP0 activated caspase 3, a key regulatory protein in the apoptotic pathway. A pro-apoptotic gene (Bax), but not bICP0, induced caspase 3 cleavage and activation by 8 h after transfection of neuro-2A cells. Conversely, bICP0 or the N-terminal 356 aa of bICP0 did not induce caspase 3 cleavage in neuro-2A cells until 30 h after transfection, suggesting that bICP0 stimulates caspase 3 cleavage by an indirect mechanism. These studies indicate that the toxic functions of bICP0 correlate with caspase 3 cleavage and activation.
Henderson
Gail
G
Department of Veterinary and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, NE 68503, USA.
Zhang
Yange
Y
Department of Veterinary and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, NE 68503, USA.
Inman
Melissa
M
Department of Veterinary and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, NE 68503, USA.
Jones
Dallas
D
Department of Veterinary and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, NE 68503, USA.
Jones
Clinton
C
Department of Veterinary and Biomedical Sciences, Nebraska Center for Virology, University of Nebraska, Lincoln, NE 68503, USA.
D000595:Amino Acid Sequence; D000818:Animals; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002417:Cattle; D004789:Enzyme Activation; D008969:Molecular Sequence Data; D015534:Trans-Activators / Q000502:physiology*; D014162:Transfection; D044767:Ubiquitin-Protein Ligases; D014764:Viral Proteins / Q000502:physiology*
D015534:Trans-Activators; D014764:Viral Proteins; D044767:Ubiquitin-Protein Ligases; C086729:bICP0 protein, Bovine herpesvirus 1; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases