Evidence map›Paper›PMID 30176164›Full record

ArticleThe Journal of general virology2018

HSV-1 DNA polymerase 3'-5' exonuclease-deficient mutant D368A exhibits severely reduced viral DNA synthesis and polymerase expression.

Jessica L Lawler, Donald M Coen

Open access · greenAbstract read
In one paragraph

Article in The Journal of general virology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 29% 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

5 citing papers in PubMed, 8 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

2 authors at 1 institution in 1 country.

Jessica L Lawler1​Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.
Donald M Coen2​PhD Program in Virology, Harvard Medical School, Boston, MA, USA.
Harvard University · US

Funding

MOLECULAR GENETICS OF HSV DNA POLYMERASE GENER01AI019838 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI COEN, DONALD M, HOGLE, JAMES M · 1985 to 2015
$5.9M
NIAID NIH HHS R01 AI019838
6 · The paper itself

Abstract

Herpesviruses, including herpes simplex virus-1, encode and express a DNA polymerase that is required for replication of their dsDNA genomes. The catalytic subunit of this enzyme contains a 3'-5' exonuclease that is involved in proofreading during replication. Although certain mutations that severely impair exonuclease activity are not lethal to the virus, it was reported that virus containing the substitution of alanine for aspartate 368 (D368A), which ablates exonuclease activity, could not be recovered, raising the possibility that this activity is essential for viral replication. To investigate this issue, we produced virus containing this mutation (D368A Pol) using a complementing cell line. D368A Pol virus was unable to form plaques on non-complementing cells. Viral DNA synthesis and polymerase activity were severely inhibited in D368A-infected cells, as was expression of the enzyme, suggesting that effects on polymerase expression rather than on exonuclease activity per se largely explain the lethal phenotype of this mutation.

Indexed as

Virus ReplicationAmino Acid SubstitutionDNA-Directed DNA PolymeraseDNA, ViralExodeoxyribonucleasesGene ExpressionHerpesvirus 1, HumanMutant ProteinsMutation, MissenseViral Plaque AssayViral ProteinsDNA-Directed DNA PolymeraseDNA polymerase, SimplexvirusDNA, ViralExodeoxyribonucleasesMutant ProteinsViral Proteins3’-5’ exonucleaseDNA polymeraseDNA replicationHerpes smplex virus-1

Identifiers

PMID30176164
PMCPMC7011708
OpenAlexW2889308922

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.