HBV Mutation Detail Information

Virus Mutation HBV Mutation W196X


Basic Characteristics of Mutations
Mutation Site W196X
Mutation Site Sentence Well known lamivudine resistant rtYM204I/VDD mutations resulted in three types of mutations in the overlapping portions of the HBsAg encoded by S‐gene, that is, I195M (Fig.2d), W196L (Fig.2e) and W196Stop (Fig.2b) in these patients.
Mutation Level Amino acid level
Mutation Type Nonsense mutation
Gene/Protein/Region S
Standardized Encoding Gene S  
Genotype/Subtype -
Viral Reference -
Functional Impact and Mechanisms
Disease Hepatitis B, Chronic    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location India
Literature Information
PMID 16928212
Title Association of core promoter mutations with viral breakthrough in chronic hepatitis B patients on long-term lamivudine therapy
Author Kazim SN,Chauhan R,Das BC,Sarin SK
Journal Journal of gastroenterology and hepatology
Journal Info 2006 Oct;21(10):1525-32
Abstract BACKGROUND AND AIM: Virologic breakthrough (VBTH) during long-term lamivudine therapy is believed to be due to the emergence of rtYM204I/VDD mutants. We observed VBTH in 17 of 67 patients receiving long-term lamivudine therapy. The YMDD mutant at the onset of VBTH and/or subsequently was seen in eight (47%) of 17 such patients. We investigated other potential loci in the viral genome contributing to VBTH. METHODS: Chronic hepatitis B (CHB) patients (n=17) on long-term (>or=12 months) lamivudine therapy who had at least one episode of VBTH were selected (group I). Age, sex, serology and baseline viral load matched patients on long-term lamivudine without VBTH (n=12) served as controls (group II). Hepatitis B virus (HBV) DNA sequences were analyzed for pre-S, surface, polymerase, core promoter, precore and core regions and were compared with sequences of respective genotypes. RESULTS: Group I patients with VBTH (n=17) either had rtYM204I/VDD mutations (n=8, group Ia YMDD) or no rtYM204I/VDD mutations (n=9, group Ib non-YMDD). Group Ia patients had median baseline HBV DNA of 2794 pg/mL (range 3-9166 pg/mL) and a mean alanine aminotransferase (ALT) level of 86+/-33 IU/L. In group Ib, the median baseline viral DNA was 916 pg/mL (range 8.3-5787 pg/mL) and the mean ALT was 61+/-38 IU/L. The first VBTH in group Ia and Ib patients was noted at 21+/-9 months and 15.2+/-5.9 months, respectively, with a rise in HBV DNA levels from undetectable limits to 952 pg/mL (range 4.3-4875 pg/mL) and 571 pg/mL (range 1.2-1970 pg/mL), respectively. Core promoter mutations were seen in five of eight (62.5%) and in six of nine (66.6%); classic double mutations (A1762T/G1764A) of core promoter region were detected in two and three patients and novel double mutations of core promoter (G1764T/C1766G) in one patient each of group Ia and Ib patients, respectively. Compared to 11 (68%) of 17 group I patients, only three (25%) of 12 patients in group II had core promoter mutations (P<0.05). No patient in group II had double mutations of the core promoter region. No significant difference in viral mutations was seen in any other region of the viral genome between group I and group II patients. In group I, none of the 15 patients (two died of hepatocellular carcinoma), but five (42%) group II patients achieved hepatitis B e antigen (HBeAg) seroconversion and sustained response by month 24 (P<0.05). CONCLUSION: Both core promoter and YMDD motif mutation(s) are associated with VBTH in patients on long-term lamivudine therapy. Whether or not these promoter mutations in the absence of YMDD mutations confer drug resistance needs to be studied in an in vitro cell culture system, as they could create novel and stronger binding sites for hepatocyte nuclear factors.
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.