HBV Mutation Detail Information

Virus Mutation HBV Mutation A1762T


Basic Characteristics of Mutations
Mutation Site A1762T
Mutation Site Sentence The A1762T/G1764A mutations, one of the most common mutations in the hepatitis B virus basal core promoter, are associated with the progression of chronic HBV infection.
Mutation Level Nucleotide level
Mutation Type Nonsynonymous substitution
Gene/Protein/Region BCP
Standardized Encoding Gene
Genotype/Subtype D
Viral Reference NC_003977.2
Functional Impact and Mechanisms
Disease Carcinoma, Hepatocellular    
Immune Y
Target Gene HNF1A   
Clinical and Epidemiological Correlations
Clinical Information -
Treatment -
Location China
Literature Information
PMID 37772469
Title The A1762T/G1764A mutations enhance HBV replication by alternating viral transcriptome
Author Yang D,Zou J,Guan G,Feng X,Zhang T,Li G,Liu H,Zheng H,Xi J,Yu G,Dai L,Lu F,Chen X
Journal Journal of medical virology
Journal Info 2023 Oct;95(10):e29129
Abstract The A1762T/G1764A mutations, one of the most common mutations in the hepatitis B virus basal core promoter, are associated with the progression of chronic HBV infection. However, effects of these mutations on HBV replication remains controversial. This study aimed to systematically investigate the effect of the mutations on HBV replication and its underlying mechanisms. Using the prcccDNA/pCMV-Cre recombinant plasmid system, a prcccDNA-A1762T/G1764A mutant plasmid was constructed. Compared with wild-type HBV, A1762T/G1764A mutant HBV showed enhanced replication ability with higher secreted HBV DNA and RNA levels, while Southern and Northern blot indicated higher intracellular levels of relaxed circular DNA, single-stranded DNA, and 3.5 kb RNA. Meanwhile, the mutations increased expression of intracellular core protein and decreased the production of HBeAg and HBsAg. In vitro infection based on HepG2-NTCP cells and mice hydrodynamic injection experiment also proved that these mutations promote HBV replication. 5'-RACE assays showed that these mutations upregulated transcription of pregenomic RNA (pgRNA) while downregulating that of preC RNA, which was further confirmed by full-length transcriptome sequencing. Moreover, a proportion of sub-pgRNAs with the potential to express polymerase were also upregulated by these mutations. The ChIP-qPCR assay showed that A1762T/G1764A mutations created a functional HNF1alpha binding site in the BCP region, and its overexpression enhanced the effect of A1762T/G1764A mutations on HBV. Our findings revealed the mechanism and importance of A1762T/G1764A mutations as an indicator for management of CHB patients, and provided HNF1alpha as a new target for curing HBV-infected patients.
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.