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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Apr 01, 2022 |
| Title |
Hepatitis B virus core protein is not required for cccDNA transcriptional regulation |
| Organisms |
Homo sapiens; Hepatitis B virus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Background & Aims: Hepatitis B virus (HBV) infection is a major health burden worldwide and currently there is no cure. The persistence of HBV covalently closed circular DNA (cccDNA) is the major obstacle for antiviral treatment. HBV core protein (HBc) has merged as a promising antiviral target, as it plays important roles in critical steps of viral life cycle. However, whether HBc could regulate HBV cccDNA transcription remains to be illustrated.
Methods: Synthesized HBV cccDNA and HBVcircle with or without HBc deficiency were transfected into hepatocytes. A recently reported Adeno-Associated Virus (AAV) mediated HBV cccDNA mouse model was employed. Two capsid assembly modulators (CAMs) were used. HBV replication markers were evaluated. Chromatin immunoprecipitation (ChIP) or ChIP sequencing assays were conducted with different transcription factors, histones and RNA polymerase 2.
Results: In HBV cccDNA and HBVcircle transfection assays, lack of HBc showed no effect on transcription of HBV RNA as well as HBV surface antigen production. Reconstitution of HBc did not change cccDNA derived HBV markers. Similar results were obtained in vivo, from mouse cccDNA model. ChIP data revealed similar transcription regulation of HBc deficient cccDNA chromatin with wide type cccDNA. Furthermore, CAMs treatment could not alter cccDNA transcription.
Conclusions: Our results indicate that HBc neither affects histone modifications and transcription factors binding of cccDNA, nor influences cccDNA transcription. Although CAMs could reduce HBc binding to cccDNA, it does not suppress cccDNA transcriptional activity. Thus, therapeutic targeting capsid or HBc is not sufficient to reduce cccDNA transcription.
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| Overall design |
eight samples were analyzed
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| Web link |
https://journals.asm.org/doi/10.1128/jvi.01362-22
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| Contributor(s) |
Xia Y, Zhong Y, Wang W, Wu C |
| Citation(s) |
36226986 |
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| Submission date |
Mar 29, 2022 |
| Last update date |
Mar 08, 2023 |
| Contact name |
Youquan Zhong |
| E-mail(s) |
2019203010049@whu.edu.cn
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| Organization name |
Wuhan University
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| Department |
TaiKang Medical School,
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| Lab |
XIA lab
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| Street address |
NO.115, Donghu road, Wuchang district, Wuhan city, Hubei province, China.
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| City |
Wuhan |
| State/province |
hubei |
| ZIP/Postal code |
430000 |
| Country |
China |
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| Platforms (1) |
| GPL32090 |
Illumina NovaSeq 6000 (Hepatitis B virus; Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA821068 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE199653_RAW.tar |
50.0 Kb |
(http)(custom) |
TAR (of BW) |
| GSE199653_reference_sequence.txt.gz |
1.1 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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