Evidence map›Paper›PMID 29649495›Full record

ArticleAntiviral research2018

A Guinea pig cytomegalovirus resistant to the DNA maturation inhibitor BDCRB.

Amine Ourahmane, Anne Sauer, Daniel E Nixon, Christine Murphy, Melissa Mondello, Erin Douglass Chiu, Stephanie Siegmund, Jian Ben Wang, Michael A McVoy

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Antiviral research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact, top 96% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Anti-CMV therapy, what next? A systematic review.Frontiers in microbiology · 2023
    Review
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

9 authors at 3 institutions in 1 country.

Amine OurahmaneDepartments of Pediatrics, Medical College of Virginia Campus of Virginia Commonwealth University, 1101 E. Marshall Street, Richmond, VA 23298-0163, USA.
Anne SauerDepartments of Pediatrics, Medical College of Virginia Campus of Virginia Commonwealth University, 1101 E. Marshall Street, Richmond, VA 23298-0163, USA.
Daniel E NixonDepartments of Medicine, Medical College of Virginia Campus of Virginia Commonwealth University, 1101 E. Marshall Street, Richmond, VA 23298-0163, USA.
Christine MurphyDepartments of Pediatrics, Medical College of Virginia Campus of Virginia Commonwealth University, 1101 E. Marshall Street, Richmond, VA 23298-0163, USA.
Melissa MondelloDepartments of Pediatrics, Medical College of Virginia Campus of Virginia Commonwealth University, 1101 E. Marshall Street, Richmond, VA 23298-0163, USA.
Erin Douglass ChiuDepartments of Pediatrics, Medical College of Virginia Campus of Virginia Commonwealth University, 1101 E. Marshall Street, Richmond, VA 23298-0163, USA.
Stephanie SiegmundGovernor's School for Government and International Studies, Richmond, VA 23230, USA.
Jian Ben WangDepartments of Pediatrics, Medical College of Virginia Campus of Virginia Commonwealth University, 1101 E. Marshall Street, Richmond, VA 23298-0163, USA.
Michael A McVoyDepartments of Pediatrics, Medical College of Virginia Campus of Virginia Commonwealth University, 1101 E. Marshall Street, Richmond, VA 23298-0163, USA. Electronic address: michael.mcvoy@vcuhealth.org.
Virginia Commonwealth University Medical Center · USOffice of the Governor · USVirginia Commonwealth University · US

Funding

HUMAN CYTOMEGALOVIRUS DNA CLEAVAGE AND PACKAGINGR01AI046668 · NIAID · VIRGINIA COMMONWEALTH UNIVERSITY · PI MCVOY, MICHAEL A · 2001 to 2005
$1.2M
Analysis of cytomegalovirus DNA cleavage/packaging genesR21AI053768 · NIAID · VIRGINIA COMMONWEALTH UNIVERSITY · PI MCVOY, MICHAEL A · 2003 to 2004
$348k
NIAID NIH HHS R01 AI046668NIAID NIH HHS R21 AI053768
6 · The paper itself

Abstract

Herpesvirus DNA packaging is an essential step in virion morphogenesis and an important target for antiviral development. The halogenated benzimidazole 2-bromo-5,6-dichloro-1-β-d-ribofuranosyl-1H-benzimidazole (BDCRB) was the first compound found to selectively disrupt DNA packaging. It has activity against human cytomegalovirus as well as guinea pig cytomegalovirus. The latter provides a useful small animal model for congenital cytomegalovirus infection. To better understand the mechanism by which BDCRB acts, a guinea pig cytomegalovirus resistant to BDCRB was derived and characterized. An L406P substitution occurred within GP89, a subunit of the complex that cleaves and packages DNA, but transfer of this mutation to an otherwise wild type genetic background did not confer significant BDCRB resistance. The resistant virus also had a 13.4-kb deletion that also appeared to be unrelated to BDCRB-resistance as a virus with a similar spontaneous deletion was sensitive to BDCRB. Lastly, the BDCRB-resistant virus exhibited a dramatic increase in the number of reiterated terminal repeats at both genomic termini. The mechanism that underlies this change in genome structure is not known but may relate to the duplication of terminal repeats that is associated with DNA cleavage and packaging. A model is presented in which BDCRB impairs the ability of terminase to recognize cleavage site sequences, but repeat arrays overcome this impairment by presenting terminase with multiple opportunities to recognize the correct cleavage site sequences that lie within the repeats. Further elucidation of this phenomenon should prove valuable for understanding the molecular basis of herpesvirus DNA maturation and the mechanism of action of this class of drugs.

Indexed as

AnimalsAntiviral AgentsBenzimidazolesCells, CulturedCytomegalovirusCytomegalovirus InfectionsDNA, ViralFibroblastsGenome, ViralGuinea PigsHydrocarbons, HalogenatedSequence Analysis, DNAVirus ReplicationAntiviral AgentsbenzimidazoleBenzimidazolesDNA, ViralHydrocarbons, HalogenatedAntiviral resistanceCytomegalovirusDNA packagingGenome maturationGenome structureHalogenated benzimidazole

Identifiers

PMID29649495
PMCPMC5955856
OpenAlexW2798104375

What OpenQuestion holds

Textmetadata
LicenceTDM
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.