HBV Mutation Detail Information

Virus Mutation HBV Mutation S219A


Basic Characteristics of Mutations
Mutation Site S219A
Mutation Site Sentence The percentage of patients with sS210R/rtS219A was comparable between drug naïve HCC-patients (33.3%, 3/9) and drug-treated HCC-patients (35.7%, 5/14), thus excluding the impact of antiviral therapy on the selection of this mutation.
Mutation Level Amino acid level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region RT
Standardized Encoding Gene P  
Genotype/Subtype -
Viral Reference X02763.1;X65259.1
Functional Impact and Mechanisms
Disease Hepatitis B, Chronic    
Immune -
Target Gene -
Clinical and Epidemiological Correlations
Clinical Information Y
Treatment -
Location -
Literature Information
PMID 28152517
Title Novel HBsAg mutations correlate with hepatocellular carcinoma, hamper HBsAg secretion and promote cell proliferation in vitro
Author Salpini R,Surdo M,Warner N,Cortese MF,Colledge D,Soppe S,Bellocchi MC,Armenia D,Carioti L,Continenza F,Di Carlo D,Saccomandi P,Mirabelli C,Pollicita M,Longo R,Romano S,Cappiello G,Spano A,Trimoulet P,Fleury H,Vecchiet J,Iapadre N,Barlattani A,Bertoli A,Mari T,Pasquazzi C,Missale G,Sarrecchia C,Orecchini E,Michienzi A,Andreoni M,Francioso S,Angelico M,Verheyen J,Ceccherini-Silberstein F,Locarnini S,Perno CF,Svicher V
Journal Oncotarget
Journal Info 2017 Feb 28;8(9):15704-15715
Abstract BACKGROUND: An impaired HBsAg-secretion can increase HBV oncogenic-properties. Here, we investigate genetic-determinants in HBsAg correlated with HBV-induced hepatocellular carcinoma (HCC), and their impact on HBsAg-secretion and cell-proliferation. METHODS: This study included 128 chronically HBV-infected patients: 23 with HCC (73.9% D; 26.1% A HBV-genotype), and 105 without cirrhosis/HCC (72.4% D, 27.6% A) as reference-group. The impact of mutations on HBsAg-secretion was assessed by measuring the ratio [secreted/intracellular HBsAg] until day 5 post-transfection. The impact of mutations on cell-cycle advancement was assessed by flow-cytometry. RESULTS: Two HBsAg mutations significantly correlated with HCC: P203Q (17.4% [4/23] in HCC vs 1.0% [1/105] in non-HCC, P=0.004); S210R (34.8% [8/23] in HCC vs 3.8% [4/105] in non-HCC, P <0.001); P203Q+S210R (17.4% [4/23] in HCC vs 0% [0/110] in non-HCC, P=0.001). Both mutations reside in trans-membrane C-terminal domain critical for HBsAg-secretion. In in-vitro experiments, P203Q, S210R and P203Q+S210R significantly reduced the ratio [secreted/intracellular HBsAg] compared to wt at each time-point analysed (P <0.05), supporting an impaired HBsAg-secretion. Furthermore, P203Q and P203Q+S210R increased the percentage of cells in S-phase compared to wt, indicating cell-cycle progression (P203Q:26+/-13%; P203Q+S210R:29+/-14%; wt:18%+/-9, P <0.01. Additionally, S210R increased the percentage of cells in G2/M-phase (26+/-8% for wt versus 33+/-6% for S210R, P <0.001). CONCLUSIONS: Specific mutations in HBsAg C-terminus significantly correlate with HBV-induced HCC. They hamper HBsAg-secretion and are associated with increased cellular proliferation, supporting their involvement in HCC-development. The identification of viral genetic markers associated with HCC is critical to identify patients at higher HCC-risk that may deserve intensive liver monitoring, and/or early anti-HBV therapy.
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.