Impact of glycoprotein B genotype and naturally occurring ORF UL56 polymorphisms upon susceptibility of clinical human cytomegalovirus isolates to letermovir

Letermovir is a novel anti-HCMV drug in Phase III development that targets the UL56 subunit of the viral terminase complex. In immunocompromised patients four major glycoprotein B (gB) subtypes are known and may influence pathogenesis and thus disease outcomes. Using a panel of 74 letermovir-naïve,...

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Bibliographic Details
Published in:Antiviral research 2016-08, Vol.132, p.204-209
Main Authors: Lischka, Peter, Zhang, Douglas, Holder, Daniel, Zimmermann, Holger
Format: Article
Language:English
Subjects:
Acetates - pharmacology
Antiviral Agents - pharmacology
Cytomegalovirus - drug effects
Cytomegalovirus - genetics
Cytomegalovirus - isolation & purification
Cytomegalovirus Infections - virology
Drug Resistance, Viral
Ganciclovir - pharmacology
Genotype
Human cytomegalovirus
Humans
Microbial Sensitivity Tests
Mutation
Polymorphism, Genetic
Polymorphism, Single Nucleotide
Quinazolines - pharmacology
Viral Envelope Proteins - genetics
Viral Structural Proteins - genetics
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Summary:Letermovir is a novel anti-HCMV drug in Phase III development that targets the UL56 subunit of the viral terminase complex. In immunocompromised patients four major glycoprotein B (gB) subtypes are known and may influence pathogenesis and thus disease outcomes. Using a panel of 74 letermovir-naïve, low-passage, clinical HCMV isolates, we examined the potential impact of i) gB genotype and ii) naturally occurring UL56 sequence variations upon susceptibility to letermovir. Our data show that letermovir’s potency is independent of gB subtype and show that naturally-occurring letermovir-resistance is rare or possibly absent. •An association between infection with a distinct HCMV gB subtype and the clinical outcome of patients has been suggested.•Letermovir is a new anti HCMV drug in Phase 3 clinical development.•The anti HCMV potency of letermovir is independent of the gB subtype.•The gene region involved in letermovir resistance is highly conserved among HCMV field isolates.
ISSN:0166-3542
1872-9096
DOI:10.1016/j.antiviral.2016.06.008