Full-length hepatitis B virus sequences from naïve patients with fluctuation of viral load during ADV monotherapy

Abstract

The reasons for adefovir dipivoxil (ADV) treatment failures appear diverse. Few studies have reported full-length hepatitis B virus (HBV) genome in patients with ADV treatment failures. The patients were from a phase III clinical trial that investigated the antiviral response to ADV in China. Seven patients had increase in HBV-DNA (>1 log(10) copies/ml above on-treatment nadir) at week 52. The serum HBV-DNA levels were above 10(4)copies/ml at week 92 in four of them. Sixteen full-length HBV genomes from the four patients at four time points were sequenced using cloning sequencing method. The frequency of substitutions at week 52 was higher than at weeks 28(16 wt) and 92(80). HBV-DNA reduction was correlated negatively with the frequency of substitutions at the three time points. No published ADV-resistant mutations were detected. The mutations, including substitutions in immunogenic epitopes and conserved sites of the polymerase gene, were frequent during ADV treatment. Amino acid deletions in X gene and basal core promoter/pre-core mutations appeared before or during ADV treatment. The substitutions in immunogenic epitopes (mainly of the surface gene) and conserved sites of the polymerase gene other than ADV-resistant mutations may have influenced antiviral efficacy in the study. More potent antiviral drugs may be important to rescue individual patients and for public health safety. It is needed to study how these substitutions influence HBV replication, disease progression, and antiviral treatment efficacy.

Molecular characterisation of hepatitis B virus in the resident Chinese population in Panama City

“…DNA bands were visualised on a 1% agarose gel. The circular PCR amplicon obtained was sequenced directly as previously reported (Li et al 2010). …”

Important Role of Hematopoietic Proteoglycan Serglycin in Liver Hepatocellular Carcinoma Associated with Tumor Microenvironment

“…It interacts with proteases, chemokines, cytokines, and is required for the formation of secretory granules [7][8][9]. The HepG2.2.15 cell line is derived from HepG2 human hepatoma cells chronically infected with HBV [10]. In our previous work, we analyzed the Human Genome U133 Plus 2.0 Array (Platform GPL570; Affymetrix, Santa Clara, CA) and showed the presence of extensive changes in global gene transcription in HepG2.215 compared with HepG2 cells.…”

“…The HepG2.2.15 cell line is derived from HepG2 human hepatoma cells chronically infected with HBV [10]. We previously analyzed the Human Genome U133 Plus 2.0 Array (Platform GPL570; Affymetrix, Santa Clara, CA) and revealed extensive changes in global gene transcription in HepG2.215 compared with HepG2 cells, with SRGN being the most significantly differentially expressed gene [11].…”

“…Serglycin (SRGN, gene SRGN) is a prominent hematopoietic proteoglycan with inflammatory and malignant properties, which interacts with proteases, chemokines, and cytokines and is required for the formation of secretory granules [7][8][9]. The HepG2.2.15 cell line is derived from HepG2 human hepatoma cells chronically infected with HBV [10]. We previously analyzed the Human Genome U133 Plus 2.0 Array (Platform GPL570; Affymetrix, Santa Clara, CA) and revealed extensive changes in global gene transcription in HepG2.215 compared with HepG2 cells, with SRGN being the most significantly differentially expressed gene [11].…”