Evidence map›Paper›PMID 24890586›Full record

ArticleAntimicrobial agents and chemotherapy2014

Improved detection of emerging drug-resistant mutant cytomegalovirus subpopulations by deep sequencing.

Sunwen Chou, Ronald J Ercolani, Malaya K Sahoo, Martina I Lefterova, Lynne M Strasfeld, Benjamin A Pinsky

Abstract readCase Reports
In one paragraph

Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

26 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Practical updates in clinical antiviral resistance testing.Journal of clinical microbiology · 2024
    Review
  6. Article
  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Definitions of Resistant and Refractory Cytomegalovirus Infection and Disease in Transplant Recipients for Use in Clinical Trials.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2019
    Article
  17. Article
  18. Cytomegalovirus resistance in CD34Transplant infectious disease : an official journal of the Transplantation Society · 2018
    Article
  19. Article
  20. 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

6 authors.

Sunwen ChouDivision of Infectious Diseases, Oregon Health Science University, Portland, Oregon, USA Department of Veterans Affairs Medical Center, Portland, Oregon, USA chous@ohsu.edu.
Ronald J ErcolaniDepartment of Veterans Affairs Medical Center, Portland, Oregon, USA.
Malaya K SahooDepartment of Pathology, Stanford University School of Medicine, Stanford, California, USA.
Martina I LefterovaDepartment of Pathology, Stanford University School of Medicine, Stanford, California, USA.
Lynne M StrasfeldDivision of Infectious Diseases, Oregon Health Science University, Portland, Oregon, USA.
Benjamin A PinskyDepartment of Pathology, Stanford University School of Medicine, Stanford, California, USA Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, California, USA.

Funding

ANTIVIRAL DRUG RESISTANCE IN HUMAN CYTOMEGALOVIRUSR01AI039938 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI CHOU, SUNWEN · 1996 to 2013
$3.4M
Alternative antiviral drug targets for human cytomegalovirus infectionI01BX000925 · VA · PORTLAND VA MEDICAL CENTER · PI CHOU, SUNWEN · 2011 to 2014
–
BLRD VA I01 BX000925NIAID NIH HHS R01 AI039938NIAID NIH HHS R01-AI39938
6 · The paper itself

Abstract

In immunosuppressed hosts, the development of multidrug resistance complicates the treatment of cytomegalovirus (CMV) infection. Improved genotypic detection of impending drug resistance may follow from recent technical advances. A severely T-cell-depleted patient with chronic lymphocytic leukemia developed CMV pneumonia and high plasma viral loads that were poorly responsive to antiviral therapy. Serial plasma specimens were analyzed for mutant viral populations by conventional and high-throughput deep-sequencing methods. Uncharacterized mutations were phenotyped for drug resistance using recombinant viruses. Conventional genotyping detected viruses with the UL97 kinase substitution C607Y after ganciclovir treatment, a transient subpopulation of UL54 polymerase L773V mutants first detected 8 weeks after foscarnet was started, and a subpopulation of a mutant with deletion of UL54 codons 981 and 982 2 months after the addition of cidofovir. Deep sequencing of the same serial specimens revealed the same UL54 mutants sooner, along with a more complex evolution of known and newly recognized mutant subpopulations missed by conventional sequencing. The UL54 exonuclease substitutions D413N, K513R, and C539G were newly shown to confer ganciclovir-cidofovir resistance, while L773V was shown to confer foscarnet resistance and add to the ganciclovir resistance conferred by UL97 C607Y. Increased sequencing depth provided a more timely and detailed diagnosis of mutant viral subpopulations that evolved with changing anti-CMV therapy.

Indexed as

Immunocompromised HostMutationAntiviral AgentsCidofovirCytomegalovirusCytomegalovirus InfectionsCytosineDNA-Directed DNA PolymeraseDrug Resistance, ViralFoscarnetGanciclovirHigh-Throughput Nucleotide SequencingHumansLeukemia, Lymphocytic, Chronic, B-CellMaleMiddle AgedAntiviral AgentsCidofovirCytosineDNA-Directed DNA PolymeraseFoscarnetGanciclovirOrganophosphonatesUL54 protein, Human herpesvirus 5Viral Proteins

Identifiers

PMID24890586
PMCPMC4135977

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.