IV Mutation Detail Information

Virus Mutation IV Mutation E119G


Basic Characteristics of Mutations
Mutation Site E119G
Mutation Site Sentence Surprisingly, laninamivir used in combination with IFN-lambda1 promoted the emergence of the E119G NA mutation five passages earlier than laninamivir alone (passage 2 versus passage 7, respectively).
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region NA
Standardized Encoding Gene NA
Genotype/Subtype H1N1
Viral Reference A/California/04/09 [A(H1N1)pdm09]
Functional Impact and Mechanisms
Disease Influenza A    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment NA inhibitors
Location -
Literature Information
PMID 32393488
Title Laninamivir-Interferon Lambda 1 Combination Treatment Promotes Resistance by Influenza A Virus More Rapidly than Laninamivir Alone
Author Adams SE,Lugovtsev VY,Kan A,Bovin NV,Donnelly RP,Ilyushina NA
Journal Antimicrobial agents and chemotherapy
Journal Info 2020 Jun 23;64(7):e00301-20
Abstract Each year, 5% to 20% of the population of the United States becomes infected with influenza A virus. Combination therapy with two or more antiviral agents has been considered a potential treatment option for influenza virus infection. However, the clinical results derived from combination treatment with two or more antiviral drugs have been variable. We examined the effectiveness of cotreatment with two distinct classes of anti-influenza drugs, i.e., neuraminidase (NA) inhibitor, laninamivir, and interferon lambda 1 (IFN-lambda1), against the emergence of drug-resistant virus variants in vitro We serially passaged pandemic A/California/04/09 [A(H1N1)pdm09] influenza virus in a human lung epithelial cell line (Calu-3) in the presence or absence of increasing concentrations of laninamivir or laninamivir plus IFN-lambda1. Surprisingly, laninamivir used in combination with IFN-lambda1 promoted the emergence of the E119G NA mutation five passages earlier than laninamivir alone (passage 2 versus passage 7, respectively). Acquisition of this mutation resulted in significantly reduced sensitivity to the NA inhibitors laninamivir ( approximately 284-fold) and zanamivir ( approximately 1,024-fold) and decreased NA enzyme catalytic activity ( approximately 5-fold) compared to the parental virus. Moreover, the E119G NA mutation emerged together with concomitant hemagglutinin (HA) mutations (T197A and D222G), which were selected more rapidly by combination treatment with laninamivir plus IFN-lambda1 (passages 2 and 3, respectively) than by laninamivir alone (passage 10). Our results show that treatment with laninamivir alone or in combination with IFN-lambda1 can lead to the emergence of drug-resistant influenza virus variants. The addition of IFN-lambda1 in combination with laninamivir may promote acquisition of drug resistance more rapidly than treatment with laninamivir alone.
Sequence Data MT423008-MT423014
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.