HBV Mutation Detail Information

Virus Mutation HBV Mutation T109L


Basic Characteristics of Mutations
Mutation Site T109L
Mutation Site Sentence In line with the lack of in vitro resistance of these substitutions for JNJ‐6379 (FC of 1.2, 0.5 and 0.1 for T109M, I105L and T109L, respectively), both patients showed pronounced declines in HBV DNA of 3.18 and 3.38 log10 IU/mL (patients #5 and #7, Figure 2E and 2C and Table 2).
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region C
Standardized Encoding Gene C  
Genotype/Subtype A;E;H
Viral Reference X02763
Functional Impact and Mechanisms
Disease Hepatitis B, Chronic    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information Y
Treatment -
Location Europe;Asia Pacific
Literature Information
PMID 32579776
Title Virology analysis of chronic hepatitis B virus-infected patients treated for 28 days with JNJ-56136379 monotherapy
Author Verbinnen T,Hodari M,Talloen W,Berke JM,Blue D,Yogaratnam J,Vandenbossche J,Shukla U,De Meyer S,Lenz O
Journal Journal of viral hepatitis
Journal Info 2020 Nov;27(11):1127-1137
Abstract Four weeks of once-daily oral JNJ-56136379 (JNJ-6379; 25, 75, 150 or 250 mg), a class-N capsid assembly modulator (CAM-N), was well tolerated with potent antiviral activity in treatment-naive, chronic hepatitis B e antigen-positive and hepatitis B e antigen-negative patients (NCT02662712). Hepatitis B virus (HBV) genome sequence analysis, using HBV DNA next-generation sequence technology, was performed, and impact of substitutions on efficacy was assessed. Analyses focused on HBV core protein amino acid positions associated with JNJ-6379 and/or other CAMs in vitro resistance, and those within the CAM-binding pocket. 31/57 patients had >/= 1 polymorphism at any of the core amino acid positions of interest, most frequently at positions 38 (32%), 105 (23%) and 109 (14%). None of these polymorphisms are known to reduce JNJ-6379 in vitro activity (fold change [FC] in 50% effective concentration <3.0). Two JNJ-6379-treated patients carried a Y118F baseline core polymorphism known to reduce JNJ-6379 activity in vitro (FC = 6.6) and had HBV DNA declines of 2.77 (75 mg) and 2.19 log(10) IU/mL (150 mg) at the end of treatment. One 75 mg JNJ-6379-treated patient had an emerging T109S substitution (FC = 1.8; HBV DNA decline 3.18 log(10) IU/mL). A 25 mg JNJ-6379-treated patient had on-treatment enrichment of Y118F variant (HBV DNA decline 2.13 log(10) IU/mL). In conclusion, baseline polymorphisms and enrichment of substitutions reducing JNJ-6379 in vitro activity were rare, with no consistent impact on virological response during a 4-week phase 1b study. Emergence of resistance to longer treatments of JNJ-6379 will be evaluated in phase 2 studies.
Sequence Data NCT02662712
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.