Evidence map›Paper›PMID 15047841›Full record

ArticleJournal of virology2004

The ribonucleotide reductase R1 homolog of murine cytomegalovirus is not a functional enzyme subunit but is required for pathogenesis.

David Lembo, Manuela Donalisio, Anders Hofer, Maura Cornaglia, Wolfram Brune, Ulrich Koszinowski, Lars Thelander, Santo Landolfo

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

58 citing papers in PubMed, 91 citations in OpenAlex.

  1. Article
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  7. GJournal of virology · 2022
    Article
  8. Revisiting Regulated Cell Death Responses in Viral Infections.International journal of molecular sciences · 2022
    Review
  9. Viral Induced Protein Aggregation: A Mechanism of Immune Evasion.International journal of molecular sciences · 2021
    Review
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  11. Article
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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 4 institutions in 3 countries.

David LemboDepartment of Public Health and Microbiology, University of Turin, Turin, Italy. david.lembo@unito.it
Manuela Donalisio
Anders Hofer
Maura Cornaglia
Wolfram Brune
Ulrich Koszinowski
Lars Thelander
Santo Landolfo
University of Turin · ITUmeå University · SELudwig-Maximilians-Universität München · DEUniversity of Würzburg · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ribonucleotide reductase (RNR) is the key enzyme in the biosynthesis of deoxyribonucleotides. Alpha- and gammaherpesviruses express a functional enzyme, since they code for both the R1 and the R2 subunits. By contrast, betaherpesviruses contain an open reading frame (ORF) with homology to R1, but an ORF for R2 is absent, suggesting that they do not express a functional RNR. The M45 protein of murine cytomegalovirus (MCMV) exhibits the sequence features of a class Ia RNR R1 subunit but lacks certain amino acid residues believed to be critical for enzymatic function. It starts to be expressed independently upon the onset of viral DNA synthesis at 12 h after infection and accumulates at later times in the cytoplasm of the infected cells. Moreover, it is associated with the virion particle. To investigate direct involvement of the virally encoded R1 subunit in ribonucleotide reduction, recombinant M45 was tested in enzyme activity assays together with cellular R1 and R2. The results indicate that M45 neither is a functional equivalent of an R1 subunit nor affects the activity or the allosteric control of the mouse enzyme. To replicate in quiescent cells, MCMV induces the expression and activity of the cellular RNR. Mutant viruses in which the M45 gene has been inactivated are avirulent in immunodeficient SCID mice and fail to replicate in their target organs. These results suggest that M45 has evolved a new function that is indispensable for virus replication and pathogenesis in vivo.

Indexed as

AnimalsBase SequenceDNA, ViralGene ExpressionGenes, ViralKineticsMiceMice, SCIDMuromegalovirusNIH 3T3 CellsRecombinant ProteinsRibonucleoside Diphosphate ReductaseRibonucleotide ReductasesSubcellular FractionsViral ProteinsVirulenceDNA, Viralm45 protein, Mouse cytomegalovirus 1Recombinant ProteinsRibonucleoside Diphosphate ReductaseRibonucleotide ReductasesRrm1 protein, mouseViral Proteins

Identifiers

PMID15047841
PMCPMC374293
OpenAlexW2058304462

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.