ArticleAntimicrobial agents and chemotherapy2018
New Locus of Drug Resistance in the Human Cytomegalovirus UL56 Gene Revealed by
Article in Antimicrobial agents and chemotherapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Artesunate repurposing for cytomegalovirus management: a systematic review of efficacy, mechanisms, and perspectives.Frontiers in cellular and infection microbiology · 2026Pooled it
- Something old, something new? Herpesvirus genome packaging examined in light of lessons from the tailed bacteriophages.Journal of virology · 2026Review
- Functional and structural insights into HCMV terminase accessory proteins pUL77 and pUL93.Journal of virology · 2025Article
- Management of Cytomegalovirus Infections in the Era of the Novel Antiviral Players, Letermovir and Maribavir.Infectious disease reports · 2024Review
- Current Perspectives on Letermovir and Maribavir for the Management of Cytomegalovirus Infection in Solid Organ Transplant Recipients.Drug design, development and therapy · 2024Review
- Letermovir Rescue Therapy in Kidney Transplant Recipients with Refractory/Resistant CMV Disease.Journal of clinical medicine · 2023Article
- Development and validation of a next-generation sequencing assay with open-access analysis software for detecting resistance-associated mutations in CMV.Journal of clinical microbiology · 2023Article
- Cytomegalovirus Anterior Uveitis: Clinical Manifestations, Diagnosis, Treatment, and Immunological Mechanisms.Viruses · 2023Review
- Cytomegalovirus in children undergoing haematopoietic stem cell transplantation: a diagnostic and therapeutic approach to antiviral resistance.Frontiers in pediatrics · 2023Review
- Relative frequency of cytomegalovirus UL56 gene mutations detected in genotypic letermovir resistance testing.Antiviral research · 2022Article
- Assessment of UL56 Mutations before Letermovir Therapy in Refractory Cytomegalovirus Transplant Recipients.Microbiology spectrum · 2022Article
- The human cytomegalovirus decathlon: Ten critical replication events provide opportunities for restriction.Frontiers in cell and developmental biology · 2022Review
- Identification and characterization of bisbenzimide compounds that inhibit human cytomegalovirus replication.The Journal of general virology · 2021Article
- Cytomegalovirus Infection and the Implications of Drug-Resistant Mutations in Pediatric Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Retrospective Study from a Tertiary Hospital in China.Infectious diseases and therapy · 2021Article
- New Insights into Human Cytomegalovirus pUL52 Structure.Viruses · 2021Article
- Regulation of the MIE Locus During HCMV Latency and Reactivation.Pathogens (Basel, Switzerland) · 2020Review
- Advances in the genotypic diagnosis of cytomegalovirus antiviral drug resistance.Antiviral research · 2020Review
- Letermovir Resistance Analysis in a Clinical Trial of Cytomegalovirus Prophylaxis for Hematopoietic Stem Cell Transplant Recipients.The Journal of infectious diseases · 2020Article
- Letermovir Resistance in Hematopoietic Stem Cell Transplant Recipients: The Risks Associated with Cytomegalovirus Prophylaxis.The Journal of infectious diseases · 2020Article
- DNA Encapsidation and Capsid Assembly Are Underexploited Antiviral Targets for the Treatment of Herpesviruses.Frontiers in microbiology · 2020Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
Abstract
Letermovir is a human cytomegalovirus (CMV) terminase inhibitor recently approved as prophylaxis in stem cell transplant recipients. In further studies of emerging drug resistance, a baseline laboratory CMV strain was serially propagated in cell culture under a combination of letermovir and ganciclovir. In eight experiments, UL56 terminase gene mutations were detected beginning at 10 passages and included novel amino acid substitutions V236A, L328V, and A365S in a region previously associated with letermovir resistance. Outside this region, the UL56 substitution C25F was detected at moderate drug concentrations in two experiments as either the first detected mutation or an addition to a preexisting V231L substitution. In all cases, mutation at UL56 codon 325 conferring absolute letermovir resistance eventually developed at a median of 20 passages. No UL97 kinase or UL54 DNA polymerase mutations relevant to ganciclovir resistance were detected until many passages after the first detection of the UL56 mutations. UL56 substitutions V236A, L328V, and A365S were shown to confer borderline or low-grade letermovir resistance, while C25F conferred a 5.4-fold increase in letermovir resistance (50% effective concentration [EC
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Registered trials
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.