IV Mutation Detail Information

Virus Mutation IV Mutation I222T


Basic Characteristics of Mutations
Mutation Site I222T
Mutation Site Sentence A conformational restriction in the influenza A virus neuraminidase binding site by R152 results in a combinational effect of I222T and H274Y on oseltamivir resistance.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region NA
Standardized Encoding Gene NA
Genotype/Subtype H1N1
Viral Reference -
Functional Impact and Mechanisms
Disease Cell line    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment oseltamivir
Location -
Literature Information
PMID 24366752
Title A conformational restriction in the influenza A virus neuraminidase binding site by R152 results in a combinational effect of I222T and H274Y on oseltamivir resistance
Author Huang L,Cao Y,Zhou J,Qin K,Zhu W,Zhu Y,Yang L,Wang D,Wei H,Shu Y
Journal Antimicrobial agents and chemotherapy
Journal Info 2014;58(3):1639-45
Abstract The I222K, I222R, and I222T substitutions in neuraminidase (NA) have been found in clinically derived 2009 pandemic influenza A/H1N1 viruses with altered susceptibilities to NA inhibitors (NAIs). The effects of these substitutions, together with the most frequently observed resistance-related substitution, H274Y, on viral fitness and resistance mechanisms were further investigated in this study. Reduced sensitivities to oseltamivir were observed in all three mutants (I222K, I222R, and I222T). Furthermore, the I222K and I222T substitutions had a combinational effect of further increasing resistance in the presence of H274Y, which might result from a conformational restriction in the NA binding site. Of note, by using molecular dynamics simulations, R152, the neighbor of T222, was observed to translate to a position closer to T222, resulting in the narrowing of the binding pocket, which otherwise only subtends the residue substitution of H274Y. Moreover, significantly attenuated NA function and viral growth abilities were found in the I222K+H274Y double mutant, while the I222T+H274Y double mutant exhibited slightly delayed growth but had a peak viral titer similar to that of the wild-type virus in MDCK cells. The relative growth advantage of the I222T mutant versus the I222K mutant and the higher frequency of I222T emerging in N1 subtype influenza viruses raise concerns necessitating close monitoring of the dual substitutions I222T and H274Y.
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.