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A Newly Identified Natural Splice Variant ASN Enhances Hepatitis B Virus Amplification
Xiumin Zhang1, Sibo Zhu1, Wei Zhu1
11 Lab of Molecular Immunology, State Key Lab of Genetic Engineering, Institute of Biomedical Sciences (IBS), School of Life Sciences, Fudan University , Shanghai, People's Republic of China .
Insights
This study identified a new hepatitis B virus (HBV) splice variant, ASN, in liver cancer patients. This variant enhances HBV replication and may influence hepatocellular carcinoma (HCC) development.
Area of Science:
- Hepatology
- Virology
- Oncology
Background:
- Chronic hepatitis B virus (HBV) infection is a leading cause of liver cirrhosis and hepatocellular carcinoma (HCC) globally.
- HBV genotypes B and C are prevalent in China.
- Increased viral load and splicing variants correlate with higher HCC risk.
Purpose of the Study:
- To investigate HBV splicing variants in HCC patients.
- To identify and characterize novel HBV splice variants.
- To assess the impact of splicing variants on HBV replication.
Main Methods:
- Analysis of 24 HCC and adjacent liver tissue samples.
- Reverse transcription-polymerase chain reaction (RT-PCR) and sequencing.
- In vitro replication assays.
Main Results:
- A novel HBV splice variant, named ASN (nucleotides 2448-489 and 910-2120 deleted), was identified.
- Higher viral load and splicing variant levels were observed in tumor tissues compared to adjacent tissues.
- The identified ASN variant demonstrated enhanced HBV replication in vitro.
Conclusions:
- HBV splicing variants, including the novel ASN variant, are present in HCC patients.
- These variants may play a role in enhancing HBV replication and potentially influencing HCC development.
- While not essential, HBV splicing variants can significantly impact viral activity.
Abstract:
Chronic hepatitis B virus (HBV) infection causes approximately one-third of all the cases of liver cirrhosis and more than three-quarters of hepatocellular carcinoma (HCC) worldwide. There are eight different genotypes (A-H) of HBV, among which B and C are the major types of HBV in China. There is a positive correlation between viral load and level of viral splicing variants and the high risk of HCC. The aim of this study was to investigate the splicing variants of HBV circulating in HCC patients. Twenty-four carcinoma and adjacent liver tissues collected from HCC patients were studied. Using reverse transcription-polymerase chain reaction (RT-PCR) and sequencing, we identified a new type of natural splice variant with nucleotides 2448-489 and 910-2120 deleted, and we named it ASN. We also found that a higher viral load and splicing variant level existed in liver carcinoma tissues compared to paracarcinoma tissues. In the investigation of our splicing variant, we found its enhancing effect on HBV replication in vitro. Although splicing variants are not essential for the replication of HBV, they may have an important influence.
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