HCMV Mutation Detail Information

Virus Mutation HCMV Mutation D542E


Basic Characteristics of Mutations
Mutation Site D542E
Mutation Site Sentence A recombinant virus with this novel D542E mutation was generated via bacterial artificial chromosome-mediated marker transfer experiments.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region UL54
Standardized Encoding Gene UL54  
Genotype/Subtype -
Viral Reference X17403
Functional Impact and Mechanisms
Disease Cell line    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment CDV;CMX001
Location -
Literature Information
PMID 23650158
Title Selection and recombinant phenotyping of a novel CMX001 and cidofovir resistance mutation in human cytomegalovirus
Author James SH,Price NB,Hartline CB,Lanier ER,Prichard MN
Journal Antimicrobial agents and chemotherapy
Journal Info 2013 Jul;57(7):3321-5
Abstract CMX001 is an orally available lipid acyclic nucleotide phosphonate that delivers high intracellular levels of cidofovir (CDV)-diphosphate and exhibits enhanced in vitro antiviral activity against a wide range of double-stranded DNA viruses, including cytomegalovirus (CMV). Mutations in the DNA polymerase of CMV that impart resistance to CDV also render the virus resistant to CMX001. Here, we report a novel resistance mutation that arose under the selective pressure of CMX001. The wild-type CMV strain AD169 was propagated in human foreskin fibroblasts under increasing concentrations of CMX001 over 10 months, and the resulting strain (named CMX001(R)) was less susceptible to CDV and CMX001 in a plaque reduction assay. Genotypic analysis of virus strain CMX001(R) via conventional sequencing of the genes encoding the CMV DNA polymerase (UL54) and UL97 kinase (UL97) demonstrated one mutation that changed the wild-type aspartate to glutamate at position 542 in UL54. A recombinant virus with this novel D542E mutation was generated via bacterial artificial chromosome-mediated marker transfer experiments. Subsequent phenotypic resistance analysis of the D542E mutant demonstrated reductions in susceptibility of greater than 10-fold to CMX001 and CDV, but no resistance to foscarnet (FOS) or ganciclovir (GCV). Analysis of replicative fitness showed that both strain CMX001(R) and the D542E mutant viruses demonstrated a smaller plaque phenotype and slower replication kinetics than their respective parent viruses. These data describe the first resistance mutation generated under the selective pressure of CMX001 and suggest that CMX001 may have a unique resistance profile associated with reduced viral replication and maintenance of sensitivity to FOS and GCV.
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.