Association of Hepatitis B Virus Covalently Closed Circular DNA and Human APOBEC3B in Hepatitis B Virus-Related Hepatocellular Carcinoma.
Chronic Hepatitis B Virus (HBV) infections can progresses to liver cirrhosis and hepatocellular carcinoma (HCC). The HBV covalently-closed circular DNA cccDNA is a key to HBV persistence, and its degradation can be induced by the cellular deaminase APOBEC3. This study aimed to measure the distribution of intrahepatic cccDNA levels and evaluate the association between levels of cccDNA and APOBEC3 in HCC patients. Among 49 HCC patients, 35 matched cancerous and contiguous noncancerous liver tissues had detectable cccDNA, and the median intrahepatic cccDNA in the cancerous tissues (CT) was significantly lower than in the contiguous noncancerous tissues (CNCT) (p = 0.0033). RCA (rolling circle amplification), followed by 3D-PCR identified positive amplification in 27 matched HCC patients. Sequence analysis indicated G to A mutations accumulated to higher levels in CT samples compared to CNCT samples, and the dinucleotide context showed preferred editing in the GpA context. Among 7 APOBEC3 genes, APOBEC3B was the only one up-regulated in cancerous tissues both at the transcriptional and protein levels (p < 0.05). This implies APOBEC3B may contribute to cccDNA editing and subsequent degradation in cancerous tissues.
Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
Xuan
X
Luo
Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
Yao
Y
Huang
Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
Yanmeng
Y
Chen
Department of Microbiology, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, People's Republic of China.
Zeng
Z
Tu
Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
Jieli
J
Hu
Department of Molecular Microbiology and Immunology, Saint Louis University Liver Center, Saint Louis University School of Medicine, Saint Louis, Missouri, United States of America.
John E
JE
Tavis
Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.|Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Zhejiang University, Hangzhou, People's Republic of China.
Ailong
A
Huang
Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Institute for Viral Hepatitis, Department of Infectious Diseases, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China.
Yuan
Y
Hu
D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000235:genetics / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000821:virology*; D016022:Case-Control Studies; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D004270:DNA, Circular / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004279:DNA, Viral / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006515:Hepatitis B virus / Q000235:genetics* / Q000378:metabolism; D019694:Hepatitis B, Chronic / Q000150:complications*; D054884:Host-Pathogen Interactions; D006801:Humans; D006868:Hydrolysis; D008099:Liver / Q000201:enzymology / Q000473:pathology / Q000821:virology; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000821:virology*; D008297:Male; D008875:Middle Aged; D015778:Minor Histocompatibility Antigens / Q000235:genetics / Q000378:metabolism*
D000956:Antigens, Viral; D004270:DNA, Circular; D004279:DNA, Viral; D015778:Minor Histocompatibility Antigens; C495794:APOBEC3B protein, human; D003564:Cytidine Deaminase