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PMID: 8396674 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The RR1 gene of herpes simplex virus type 1 is uniquely trans activated by ICP0 during infection.

Journal of virology ·Vol. 67 ·No. 10 ·1993-10-00 ·Pages 6125-35

Desai P, Ramakrishnan R, Lin ZW, Osak B, Glorioso JC, Levine M

Abstract

As has been demonstrated for herpes simplex virus type 2, we show in this report that the herpes simplex virus type 1 ribonucleotide reductase large subunit (RR1) gene is trans activated in transient transfection assays by VP16 and ICP0 but not by ICP4. Deletion analysis demonstrated that responsiveness to induction to VP16 resides in an octamer/TAATGARAT sequence of the RR1 promoter and that the TATA box alone is sufficient to provide induction by ICP0. The induction of the RR1 gene by ICP0 but not by ICP4 suggested that it might be possible to identify the cis-acting element(s) responsive to ICP4 in an ICP4-inducible promoter. To this end, a series of chimeric promoters containing various portions of the regulatory sequences of the RR1 promoter and thymidine kinase (TK) promoter were constructed. The TK promoter is trans activated by both ICP0 and ICP4 in transient transfection assays and by ICP4 in infection. The data show that replacing the RR1 TATA region with the TK TATA region permits ICP4 inducibility even if the rest of the RR1 promoter elements remain intact. To test whether the RR1 gene is induced by ICP0 during infection, four mutant viruses were constructed. (i) TAATGARAT+ has the wild-type RR1 promoter driving chloramphenicol acetyltransferase (CAT) and the RR2 promoter driving the lacZ gene. The RR2 gene codes for the small subunit of the ribonucleotide reductase and is expressed as a beta gene. (ii) TAATGARAT- has a triple-base change in the octamer/TAATGARAT element which renders it unresponsive to VP16 trans activation, eliminating that portion of the activation of the RR1 gene. (iii) TAATGARAT- delta alpha 0 has a deletion of the alpha 0 gene. (iv) TAATGARAT- delta alpha 4 has a deletion of the alpha 4 gene. Infections were carried out in Vero cells at a multiplicity of infection of 10 per cell; cells were assayed for CAT and beta-galactosidase (beta-Gal) activities and for virus yields. The first two infections gave strong CAT and beta-Gal activities and high yields of progeny virus. Infection with the third virus showed no CAT activity but did produce high levels of beta-Gal activity and virus progeny. The fourth infection resulted in strong CAT activity but no beta-Gal activity or progeny virus. The data demonstrated that the RR1 promoter was activated in the absence of ICP4 but not in the absence of ICP0 in these infections.(ABSTRACT TRUNCATED AT 400 WORDS)

Related Genes
RR1
MeSH Terms
Animals Base Sequence Chloramphenicol O-Acetyltransferase/biosynthesis,genetics,metabolism Gene Deletion Genes, Viral Immediate-Early Proteins Macromolecular Substances Molecular Sequence Data Mutagenesis, Insertional Plasmids Promoter Regions, Genetic Recombinant Fusion Proteins/biosynthesis,metabolism Restriction Mapping Ribonucleotide Reductases/biosynthesis,genetics,metabolism Simplexvirus/enzymology,genetics TATA Box Transcriptional Activation Transfection Ubiquitin-Protein Ligases Vero Cells Viral Proteins/metabolism
Chemicals
Immediate-Early Proteins Macromolecular Substances Recombinant Fusion Proteins Viral Proteins Ribonucleotide Reductases Chloramphenicol O-Acetyltransferase Ubiquitin-Protein Ligases Vmw110 protein, Human herpesvirus 1
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Desai P
Department of Human Genetics, University of Michigan, Ann Arbor 48109-0618.
Ramakrishnan R
Lin Z W
Osak B
Glorioso J C
Levine M
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.67.10.6125-6135.1993
Published
1993-10-00
Pages
6125-35
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC238035
Subset
IM
Grants
NIAID NIH HHS · R01 AI8228 · United States
Corrections
ErratumIn
-
External Links
PubMed source DOI: 10.1128/JVI.67.10.6125-6135.1993 PMC Full Text View journal details
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