Evidence map›Paper›PMID 12829822›Full record

ArticleJournal of virology2003

Drug resistance patterns of recombinant herpes simplex virus DNA polymerase mutants generated with a set of overlapping cosmids and plasmids.

Julie Bestman-Smith, Guy Boivin

Open access · greenAbstract readEvaluation Study
In one paragraph

Article in Journal of virology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

33 citing papers in PubMed, 89 citations in OpenAlex.

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  11. Antiviral Drugs Against Herpesviruses.Advances in experimental medicine and biology · 2021
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  15. Complex management of resistant oral herpes simplex virus infection following hematopoietic stem cell transplantation: potential role of topical cidofovir.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2016
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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 2 institutions in 1 country.

Julie Bestman-SmithCentre de Recherche en Infectiologie, Centre Hospitalier Universitaire de Québec (Pavillon CHUL) and Université Laval, 2705 Boulevard Laurier, Ste-Foy, Québec, Canada G1V 4G2.
Guy Boivin
Centre hospitalier universitaire de Québec · CAUniversité Laval · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Herpes simplex virus (HSV) DNA polymerase (Pol) mutations can confer resistance to all currently available antiherpetic drugs. However, discrimination between mutations responsible for drug resistance and those that are part of viral polymorphism can be difficult with current methodologies. A new system is reported for rapid generation of recombinant HSV type 1 (HSV-1) DNA Pol mutants based on transfection of a set of overlapping viral cosmids and plasmids. With this approach, twenty HSV-1 recombinants with single or dual mutations within the DNA pol gene were successfully generated and subsequently evaluated for their susceptibilities to acyclovir (ACV), foscarnet (FOS), cidofovir (CDV), and adefovir (ADV). Mutations within DNA Pol conserved regions II (A719T and S724N), VI (L778M, D780N, and L782I), and I (F891C) were shown to induce cross-resistance to ACV, FOS, and ADV, with two of these mutations (S724N and L778M) also conferring significant reduction in CDV susceptibility. Mutant F891C was associated with the highest levels of resistance towards ACV and FOS and was strongly impaired in its replication capacity. One mutation (D907V) lying outside of the conserved regions was also associated with this ACV-, FOS-, and ADV-resistant phenotype. Some mutations (K522E and Y577H) within the delta-region C were lethal, whereas others (P561S and V573M) induced no resistance to any of the drugs tested. Recombinants harboring mutations within conserved regions V (N961K) and VII (Y941H) were resistant to ACV but susceptible to FOS. Finally, mutations within conserved region III were associated with various susceptibility profiles. This new system allows a rapid and accurate evaluation of the functional role of various DNA Pol mutations, which should translate into improved management of drug-resistant HSV infections.

Indexed as

MutationRecombination, GeneticAnimalsAntiviral AgentsChlorocebus aethiopsCosmidsDNA-Directed DNA PolymeraseDrug Resistance, ViralExodeoxyribonucleasesHerpesvirus 1, HumanHumansMicrobial Sensitivity TestsMutagenesis, Site-DirectedPlasmidsVero CellsViral ProteinsAntiviral AgentsDNA-Directed DNA PolymeraseDNA polymerase, SimplexvirusExodeoxyribonucleasesViral Proteins

Identifiers

PMID12829822
PMCPMC161916
OpenAlexW2166377280

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.