Evidence map›Paper›PMID 9621055›Full record

ArticleJournal of virology1998

Characterization of drug resistance-associated mutations in the human cytomegalovirus DNA polymerase gene by using recombinant mutant viruses generated from overlapping DNA fragments.

T Cihlar, M D Fuller, J M Cherrington

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed
5.7field-weighted citation impact, top 4% 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

55 citing papers in PubMed, 157 citations in OpenAlex.

  1. Trial
  2. Host DNA repair factors empower a mechanism of antiviral nucleoside analog resistance.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  17. Antiviral Drug- and Multidrug Resistance in Cytomegalovirus Infected SCT Patients.Computational and structural biotechnology journal · 2015
    Review
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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

3 authors at 1 institution in 1 country.

T CihlarGilead Sciences, Foster City, California 94404, USA. Tomas_Cihlar@gilead.com
M D Fuller
J M Cherrington
Gilead Sciences (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A number of specific point mutations in the human cytomegalovirus (HCMV) DNA polymerase (UL54) gene have been tentatively associated with decreased susceptibility to antiviral agents and consequently with clinical failure. To precisely determine the roles of UL54 mutations in HCMV drug resistance, recombinant UL54 mutant viruses were generated by using cotransfection of nine overlapping HCMV DNA fragments into permissive fibroblasts, and their drug susceptibility profiles were determined. Amino acid substitutions located in UL54 conserved region IV (N408D, F412C, and F412V), region V (A987G), and delta-region C (L501I, K513E, P522S, and L545S) conferred various levels of resistance to cidofovir and ganciclovir. Mutations in region II (T700A and V715M) and region VI (V781I) were associated with resistance to foscarnet and adefovir. The region II mutations also conferred moderate resistance to lobucavir. In contrast to mutations in other UL54 conserved regions, those residing specifically in region III (L802M, K805Q, and T821I) were associated with various drug susceptibility profiles. Mutations located outside the known UL54 conserved regions (S676G and V759M) did not confer any significant changes in HCMV drug susceptibility. Predominantly an additive effect of multiple UL54 mutations with respect to the final drug resistance phenotype was demonstrated. Finally, the influence of selected UL54 mutations on the susceptibility of viral DNA replication to antiviral drugs was characterized by using a transient-transfection-plus-infection assay. Results of this work exemplify specific roles of the UL54 conserved regions in the development of HCMV drug resistance and may help guide optimization of HCMV therapy.

Indexed as

Genes, ViralOrganophosphonatesAntiviral AgentsCidofovirCytomegalovirusCytosineDNA-Directed DNA PolymeraseDNA ReplicationDNA, ViralDrug Resistance, MicrobialFoscarnetGanciclovirHumansMutationOrganophosphorus CompoundsRecombination, GeneticAntiviral AgentsCidofovirCytosineDNA-Directed DNA PolymeraseDNA, ViralFoscarnetGanciclovirOrganophosphonatesOrganophosphorus Compounds

Identifiers

PMID9621055
PMCPMC110397
OpenAlexW2114786252

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.