IV Mutation Detail Information

Virus Mutation IV Mutation I221L


Basic Characteristics of Mutations
Mutation Site I221L
Mutation Site Sentence A novel I221L substitution in neuraminidase confers high-level resistance to oseltamivir in influenza B viruses.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region NA
Standardized Encoding Gene NA
Genotype/Subtype -
Viral Reference B/Brisbane/60/2008 wild type
Functional Impact and Mechanisms
Disease Influenza B    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment oseltamivir;zanamivir
Location France
Literature Information
PMID 24795482
Title A novel I221L substitution in neuraminidase confers high-level resistance to oseltamivir in influenza B viruses
Author Escuret V,Collins PJ,Casalegno JS,Vachieri SG,Cattle N,Ferraris O,Sabatier M,Frobert E,Caro V,Skehel JJ,Gamblin S,Valla F,Valette M,Ottmann M,McCauley JW,Daniels RS,Lina B
Journal The Journal of infectious diseases
Journal Info 2014 Oct 15;210(8):1260-9
Abstract Influenza B viruses with a novel I221L substitution in neuraminidase (NA) conferring high-level resistance to oseltamivir were isolated from an immunocompromised patient after prolonged oseltamivir treatment. METHODS: Enzymatic characterization of the NAs (Km, Ki) and the in vitro fitness of viruses carrying wild-type or mutated (I221L) NA genes were evaluated. Proportions of wild-type and mutated NA genes were directly quantified in the patient samples. Structural characterizations by X-ray crystallography of a wild-type and I221L variant NA were performed. RESULTS: The Km and Ki revealed that the I221L variant NA had approximately 84 and 51 times lower affinity for oseltamivir carboxylate and zanamivir, respectively, compared with wild-type NA. Viruses with a wild-type or I221L variant NA had similar growth kinetics in Madin-Darby canine kidney (MDCK) cells, and 5 passages in MDCK cells revealed no reversion of the I221L substitution. The crystal structure of the I221L NA and oseltamivir complex showed that the leucine side chain protrudes into the hydrophobic pocket of the active site that accommodates the pentyloxy substituent of oseltamivir. CONCLUSIONS: Enzyme kinetic and NA structural analyses provide an explanation for the high level of resistance to oseltamivir while retaining good fitness of viruses carrying I221L variant NA.
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.