A Newly Identified Natural Splice Variant ASN Enhances Hepatitis B Virus Amplification.
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.
1 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 .
Xiumin
X
Zhang
1 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 .
Sibo
S
Zhu
1 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 .
Wei
W
Zhu
2 Oriental Liver Surgery Hospital, Second Military Medical University , Shanghai, People's Republic of China .
Aijun
A
Li
1 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 .
Naishuo
N
Zhu
D017398:Alternative Splicing / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000821:virology*; D045744:Cell Line, Tumor; D004279:DNA, Viral / Q000235:genetics*; D005838:Genotype; D056945:Hep G2 Cells; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis; D006513:Hepatitis B e Antigens / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000821:virology*; D006801:Humans; D008099:Liver / Q000821:virology; D008113:Liver Neoplasms / Q000821:virology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019562:Viral Load / Q000235:genetics
D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens