HCMV Mutation Detail Information

Virus Mutation HCMV Mutation L257I


Basic Characteristics of Mutations
Mutation Site L257I
Mutation Site Sentence With terminase modelling, we make the hypothesis that LMV could bind to domains were UL56-L257I and UL51-A95V mutations were localized.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region UL56
Standardized Encoding Gene UL56  
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease Cytomegalovirus infections    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location -
Literature Information
PMID 35690130
Title First clinical description of letermovir resistance mutation in cytomegalovirus UL51 gene and potential impact on the terminase complex structure
Author Muller C,Tilloy V,Frobert E,Feghoul L,Garrigue I,Lepiller Q,Mirand A,Sidorov E,Hantz S,Alain S
Journal Antiviral research
Journal Info 2022 Aug;204:105361
Abstract BACKGROUND: Letermovir (LMV) is a human cytomegalovirus (HCMV) terminase inhibitor indicated as prophylaxis for HCMV-positive stem-cell recipients. Its mechanism of action involves at least the viral terminase proteins pUL56, pUL89 and pUL51. Despite its efficiency, resistance mutations were characterized in vitro and in vivo, largely focused on pUL56. To date, mutations in pUL51 in clinical resistance remain to be demonstrated. METHODS: The pUL51 natural polymorphism was described by sequencing 54 LMV-naive strains and was compared to UL51 HCMV genes from 16 patients non-responding to LMV therapy (prophylaxis or curative). Recombinant viruses were built by <> mutagenesis to measure the impact of the new mutations on antiviral activity and viral growth. Structure prediction was performed by homology modeling. The pUL51 final-model was analyzed and aligned with the atomic coordinates of the monomeric HSV-1 terminase complex (PDB:6M5R). RESULTS: Among the 16 strains from treated-patients with LMV, 4 never described substitutions in pUL51 (D12E, 17del, A95V, V113L) were highlighted. These substitutions had no impact on viral fitness. Only UL51-A95V conferred 13.8-fold increased LMV resistance level by itself (IC50 = 29.246 +/- 0.788). CONCLUSION: As an isolated mutation in pUL51 in a clinical isolate can lead to LMV resistance, genotyping for resistance should involve sequencing of the pUL51, pUL56 and pUL89 genes. With terminase modelling, we make the hypothesis that LMV could bind to domains were UL56-L257I and UL51-A95V mutations were localized.
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.