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PMID: 9765459 Published · ppublish English Journal Article

The PK domain of the large subunit of herpes simplex virus type 2 ribonucleotide reductase (ICP10) is required for immediate-early gene expression and virus growth.

Journal of virology ·Vol. 72 ·No. 11 ·1998-11-00 ·Pages 9131-41

Smith CC, Peng T, Kulka M, Aurelian L

Abstract

The large subunit of herpes simplex virus (HSV) ribonucleotide reductase (RR), RR1, contains a unique amino-terminal domain which has serine/threonine protein kinase (PK) activity. To examine the role of the PK activity in virus replication, we studied an HSV type 2 (HSV-2) mutant with a deletion in the RR1 PK domain (ICP10DeltaPK). ICP10DeltaPK expressed a 95-kDa RR1 protein (p95) which was PK negative but retained the ability to complex with the small RR subunit, RR2. Its RR activity was similar to that of HSV-2. In dividing cells, onset of virus growth was delayed, with replication initiating at 10 to 15 h postinfection, depending on the multiplicity of infection. In addition to the delayed growth onset, virus replication was significantly impaired (1,000-fold lower titers) in nondividing cells, and plaque-forming ability was severely compromised. The RR1 protein expressed by a revertant virus [HSV-2(R)] was structurally and functionally similar to the wild-type protein, and the virus had wild-type growth and plaque-forming properties. The growth of the ICP10DeltaPK virus and its plaque-forming potential were restored to wild-type levels in cells that constitutively express ICP10. Immediate-early (IE) genes for ICP4, ICP27, and ICP22 were not expressed in Vero cells infected with ICP10DeltaPK early in infection or in the presence of cycloheximide, and the levels of ICP0 and p95 were significantly (three- to sevenfold) lower than those in HSV-2- or HSV-2(R)-infected cells. IE gene expression was similar to that of the wild-type virus in cells that constitutively express ICP10. The data indicate that ICP10 PK is required for early expression of the viral regulatory IE genes and, consequently, for timely initiation of the protein cascade and HSV-2 growth in cultured cells.

MeSH Terms
Animals Base Sequence Capsid/metabolism Cell Division Cell Nucleus/virology Chlorocebus aethiops Cycloheximide/pharmacology Gene Expression/drug effects Genes, Immediate-Early Herpesvirus 2, Human/enzymology,genetics,growth & development Oligonucleotide Probes/genetics Protein Biosynthesis Protein Conformation Protein Serine-Threonine Kinases/chemistry,genetics,metabolism Protein Synthesis Inhibitors/pharmacology Ribonucleotide Reductases/chemistry,genetics,metabolism Sequence Deletion Vero Cells Viral Plaque Assay Virus Replication
Chemicals
Oligonucleotide Probes Protein Synthesis Inhibitors Cycloheximide ICP10 protein, herpes simplex virus type 2 Ribonucleotide Reductases Protein Serine-Threonine Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Smith C C
Virology/Immunology Laboratories, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Peng T
Kulka M
Aurelian L
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.72.11.9131-9141.1998
Published
1998-11-00
Pages
9131-41
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC110331
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.72.11.9131-9141.1998 PMC Full Text View journal details
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