HCMV Mutation Detail Information

Virus Mutation HCMV Mutation L595W


Basic Characteristics of Mutations
Mutation Site L595W
Mutation Site Sentence Alternative UL97 substitutions at codons 594 and 595, such as A594P and A594T, or L595F and L595W, also conferred ganciclovir EC50 increases in the 5- to 10-fold range.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region UL97
Standardized Encoding Gene UL97  
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease Cell line    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment ganciclovir
Location -
Literature Information
PMID 38163624
Title Ganciclovir and maribavir cross-resistance revisited: Relative drug susceptibilities of canonical cytomegalovirus mutants
Author Chou S,Watanabe J
Journal Antiviral research
Journal Info 2024 Feb;222:105792
Abstract Therapeutic use of maribavir for human cytomegalovirus infection has renewed attention to the extent of cross-resistance with ganciclovir as the existing standard therapy. Each drug selects in vivo for a characteristic set of resistance mutations in the viral UL97 kinase gene. To improve the calibration of relative susceptibilities to each drug, genetic variants at relevant UL97 codons were extensively phenotyped using the same baseline viral clone, cell culture conditions and growth readout. Ganciclovir-selected mutations at codons 460, 520, 592, 594, 595 and 603 conferred 2.8-fold (C603Y) to 12-fold (M460I) increases in ganciclovir 50% inhibitory concentrations (EC50) over wild type baseline, while conferring maribavir EC50 fold changes ranging from 0.21-fold (M460I) to 1.9-fold (A594V). Maribavir-selected mutations at codons 409, 411 and 480 conferred maribavir EC50 fold changes ranging from 17 (H411Y) to 210 (C480F), while conferring ganciclovir EC50 fold changes ranging from 0.7 (H411Y) to 2.3 (C480F). The P-loop substitution F342Y, selected by either drug, is confirmed to confer 4.7-fold and 6-fold increases in maribavir and ganciclovir EC50s respectively, and suggests this part of the ATP-binding domain of UL97 to be involved in moderate resistance to both drugs. The maribavir hypersensitivity of M460I and M460V may be advantageous.
Sequence Data -
Mutation Information
Note
Basic Characteristics of Mutations
  • Mutation Site: The specific location in a gene or protein sequence where a change occurs.
  • Mutation Level: The level at which a mutation occurs, including the nucleotide or amino acid level.
  • Mutation Type: The nature of the mutation, such as missense mutation, nonsense mutation, synonymous mutation, etc.
  • Gene/Protein/Region: Refers to the specific region of the virus where the mutation occurs. Including viral genes, viral proteins, or a specific viral genome region. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main
  • Gene/Protein/Region studied in the article is marked.
  • Genotype/Subtype: Refers to the viral genotype or subtype where the mutation occurs. If the article does not specifically indicate the relationship between the mutation and its correspondence, the main Genotype/Subtype studied in the article is marked.
  • Viral Reference: Refers to the standard virus strain used to compare and analyze viral sequences.
Functional Impact and Mechanisms
  • Disease: An abnormal physiological state with specific symptoms and signs caused by viral infection.
  • Immune: The article focuses on the study of mutations and immune.
  • Target Gene: Host genes that viral mutations may affect.
Clinical and Epidemiological Correlations
  • Clinical Information: The study is a clinical or epidemiological study and provides basic information about the population.
  • Treatment: The study mentioned a certain treatment method, such as drug resistance caused by mutations. If the study does not specifically indicate the relationship between mutations and their correspondence treatment, the main treatment studied in the article is marked.
  • Location: The source of the research data.
Literature Information
  • Sequence Data: The study provides the data accession number.