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PMID: 8151771 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cooperativity among herpes simplex virus type 1 immediate-early regulatory proteins: ICP4 and ICP27 affect the intracellular localization of ICP0.

Journal of virology ·Vol. 68 ·No. 5 ·1994-05-00 ·Pages 3027-40

Zhu Z, Cai W, Schaffer PA

Abstract

The results of transient expression assays and studies of viral mutants have shown that three of the five immediate-early proteins of herpes simplex virus type 1 (HSV-1) perform regulatory functions, individually and cooperatively. As part of efforts designed to explore the molecular basis for the functional cooperativity among ICP0, ICP4, and ICP27 in the regulation of HSV gene expression, we have examined the intracellular localization of ICP0 in cells infected with ICP4 and ICP27 null mutant viruses by indirect immunofluorescence. Although ICP0 was localized predominantly to the nuclei of wild-type virus-infected cells, it was found exclusively in the nuclei of ICP27 mutant-infected cells and in both the cytoplasm and nuclei of ICP4 mutant-infected cells, the cytoplasmic component being especially strong. These observations indicate that both ICP4 and ICP27 can affect the intracellular localization of ICP0. Transient expression assays with plasmids that express wild-type and mutant forms of ICP0, ICP4, and ICP27 confirmed that ICP4 promotes and that ICP27 inhibits the nuclear localization of ICP0. These results confirm the observations made for mutant virus-infected cells and indicate that the localization pattern seen in infected cells can be established by these three immediate-early proteins exclusive of other viral proteins. The C-terminal half of ICP27 was shown to be required to achieve its inhibitory effect on the nuclear localization of ICP0. The region of ICP0 responsive to ICP27 was mapped to the C terminus of the molecule between amino acid residues 720 and 769. In addition, the concentration of ICP27 was shown to have a significant effect on the intracellular localization of ICP0. Because the major regulatory activities of ICP0, ICP4, and ICP27 are expressed in the nucleus, the ability of these three proteins collectively to determine their own localization patterns within cells adds a new dimension to the complex process of viral gene regulation in HSV.

MeSH Terms
Animals Antibodies, Monoclonal Antibodies, Viral Cell Compartmentation Cell Nucleus/metabolism Fluorescent Antibody Technique Herpesvirus 1, Human/genetics,metabolism Immediate-Early Proteins/genetics,isolation & purification,metabolism Immunoblotting Plasmids/genetics Recombinant Proteins/metabolism Structure-Activity Relationship Transcription, Genetic Transfection Ubiquitin-Protein Ligases Vero Cells Viral Proteins/genetics,metabolism Viral Regulatory and Accessory Proteins/metabolism
Chemicals
Antibodies, Monoclonal Antibodies, Viral ICP27 protein, human herpesvirus 1 Immediate-Early Proteins Recombinant Proteins Viral Proteins Viral Regulatory and Accessory Proteins herpes simplex virus, type 1 protein ICP4 Ubiquitin-Protein Ligases Vmw110 protein, Human herpesvirus 1
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Zhu Z
Division of Molecular Genetics, Dana-Farber Cancer Institute, Boston, Massachusetts.
Cai W
Schaffer P A
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.68.5.3027-3040.1994
Published
1994-05-00
Pages
3027-40
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC236793
Subset
IM
Grants
NCI NIH HHS · R37 CA20260 · United States
External Links
PubMed source DOI: 10.1128/JVI.68.5.3027-3040.1994 PMC Full Text View journal details
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