Role of cellular phosphatase cdc25C in herpes simplex virus 1 replication.
Earlier studies have shown that in herpes simplex virus 1-infected cells, ICP22 upregulates the accumulation of a subset of gamma(2) proteins exemplified by the products of the U(L)38, U(L)41, and U(S)11 genes. The ICP22-dependent process involves degradation of cyclins A and B1, the stabilization and activation of cdc2, physical interaction of activated cdc2 with the U(L)42 DNA synthesis processivity factor, and recruitment and phosphorylation of topoisomerase IIalpha by the cdc2/U(L)42 complex. Activation of cdc2, the first step in the process, is a key function of the mitotic phosphatase cdc25C. To define the role of cdc25C, we probed some features of the ICP22-dependent pathway of upregulation of gamma(2) genes in cdc25C(-/-) cells and in cdc25C(+/+) cells derived from sibling mice. We report that cyclin B1 turned over in cdc25C(+/+) or cdc25C(-/-) cells at the same rate, that cdc2 increased in amount, and that U(S)11 and U(L)38 proteins and infectious virus accumulated in smaller amounts than in wild-type infected cells. The reduction in U(L)38 protein accumulation and virus was greater in cdc25C(-/-) cells infected with virus lacking ICP22 than in cells infected with wild-type virus. We conclude that cdc25C phosphatase plays a role in viral replication and that this role extends beyond its function of activating cdc2 for initiation of the ICP22-dependent cascade for upregulation of gamma(2) gene expression.
Smith-Donald
Benjamin A
BA
The University of Chicago, Marjorie B. Kovler Viral Oncology Laboratories, 910 East 58th St., Chicago, IL 60637. bernard.roizman@bsd.uchicago.edu.
Durand
Lizette O
LO
Roizman
Bernard
B
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D036022:Capsid Proteins; D002460:Cell Line; D002478:Cells, Cultured; D015967:Gene Expression Regulation, Viral; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology*; D051379:Mice; D016601:RNA-Binding Proteins; D015854:Up-Regulation; D014764:Viral Proteins / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins / Q000502:physiology*; D014779:Virus Replication / Q000235:genetics*; D020687:cdc25 Phosphatases / Q000502:physiology*
D036022:Capsid Proteins; C057294:ICP22 protein, human herpesvirus 1; D017874:Immediate-Early Proteins; D016601:RNA-Binding Proteins; C074546:US11 protein, herpesvirus; C081688:Ul41 protein, Human herpesvirus 1; C082563:VP19 protein, Human herpesvirus 1; D014764:Viral Proteins; D054334:Viral Regulatory and Accessory Proteins; D016203:CDC2 Protein Kinase; D020687:cdc25 Phosphatases