Evidence map›Paper›PMID 10799571›Full record

ArticleJournal of virology2000

Murine cytomegalovirus stimulates cellular thymidylate synthase gene expression in quiescent cells and requires the enzyme for replication.

G Gribaudo, L Riera, D Lembo, M De Andrea, M Gariglio, T L Rudge, L F Johnson, S Landolfo

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
4.3field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 45 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 2 countries.

G GribaudoDepartment of Public Health and Microbiology, University of Turin, Turin, Italy. gribaudo@molinette.unito.it
L Riera
D Lembo
M De Andrea
M Gariglio
T L Rudge
L F Johnson
S Landolfo
University of Turin · ITThe Ohio State University · US

Funding

Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Tasleem J Padamsee · 1985 to 2026
$132.3M
THYMIDYLATE SYNTHETASE GENE STRUCTURE AND EXPRESSIONR01GM029356 · NIGMS · OHIO STATE UNIVERSITY · PI JOHNSON, LEE F · 1985 to 2002
$762k
CARCINOGENESIS, MOLECULAR AND CELLULAR BIOLOGYT32CA009498 · NCI · OHIO STATE UNIVERSITY · PI ROBERTSON, FREDIKA M · 1985 to 2000
$109k
NCI NIH HHS CA16058NCI NIH HHS P30 CA016058NCI NIH HHS T32 CA009498NCI NIH HHS T32 CA09498NIGMS NIH HHS GM29356
6 · The paper itself

Abstract

Herpesviruses accomplish DNA replication either by expressing their own deoxyribonucleotide biosynthetic genes or by stimulating the expression of the corresponding cellular genes. Cytomegalovirus (CMV) has adopted the latter strategy to allow efficient replication in quiescent cells. In the present report, we show that murine CMV (MCMV) infection of quiescent fibroblasts induces both mRNA and protein corresponding to the cellular thymidylate synthase (TS) gene, which encodes the enzyme that catalyzes the de novo synthesis of thymidylic acid. The increase in TS gene expression was due to an increase in gene transcription, since the activity of a reporter gene driven by the mouse TS promoter was induced following MCMV infection. Mutagenesis of the potential E2F-responsive element immediately upstream from the TS essential promoter region abolished the virus-mediated stimulation of the TS promoter, suggesting that the transactivating activity of MCMV infection was E2F dependent. Cotransfection experiments revealed that expression of the viral immediate-early 1 protein was sufficient to mediate the increase in TS promoter activity. Finally, MCMV replication and viral DNA synthesis were found to be inhibited by ZD1694, a quinazoline-based folate analog that inhibits TS activity. These results demonstrate that upregulation of cellular TS expression is required for efficient MCMV replication in quiescent cells.

Indexed as

Carrier ProteinsCell Cycle ProteinsDNA-Binding ProteinsDNA ReplicationGene Expression Regulation, EnzymologicTranscriptional ActivationViral Proteins3T3 CellsAnimalsBinding SitesDNA, ViralE2F Transcription FactorsEnzyme InhibitorsHumansImmediate-Early ProteinsMiceArid4a protein, mouseCarrier ProteinsCell Cycle ProteinsDNA-Binding ProteinsDNA, ViralE2F Transcription FactorsEnzyme InhibitorsIE1 protein, cytomegalovirusImmediate-Early ProteinsQuinazolinesraltitrexedRetinoblastoma-Binding Protein 1ThiophenesThymidylate SynthaseTranscription Factor DP1Transcription FactorsViral Proteins

Identifiers

PMID10799571
PMCPMC110849
OpenAlexW2153565075

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.