Infected cell protein No. 22 is subject to proteolytic cleavage by caspases activated by a mutant that induces apoptosis.
Earlier reports have shown that the d120 mutant of herpes simplex virus 1 lacking both copies of the gene encoding the infected cells protein No. 4 (ICP4) induces apoptosis in a variety of cell lines. The programmed cell death induced by this mutant is blocked by overexpression of Bcl-2 or by transduction of infected cells with the gene encoding the viral U(S)3 protein kinase. HEp-2 cells infected with the d120 mutant express predominantly alpha proteins. Studies on these proteins revealed the accumulation of a M(r) 37,500 protein that reacted with antibody directed against the carboxyl-terminal domain of ICP22. We report that the M(r) 37,500 protein is a product of the proteolytic cleavage of ICP22 by a caspase activated by the d120 mutant. Thus the accumulation of the M(r) 37,500 protein was blocked in cells transduced with the U(S)3 protein kinase, in cells overexpressing Bcl-2, or in infected cells treated with the general caspase inhibitor zVAD-fmk. Exposure of ICP22 made in wild-type virus-infected cells to caspase 3 yielded two polypeptides, of which one could not be differentiated from the M(r) 37,500 protein with respect to electrophoretic mobility. We conclude that the cellular apoptotic response targets at least one viral protein for destruction.
Munger
Joshua
J
The Marjorie B. Kovler Viral Oncology Laboratories, The University of Chicago, Illinois 60637, USA.
Hagglund
Ryan
R
Roizman
Bernard
B
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000502:physiology*; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism*; D008970:Molecular Weight; D009154:Mutation; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins
D000590:Amino Acid Chloromethyl Ketones; C057294:ICP22 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C078424:EUS1 protein, Equine herpesvirus 1; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases