 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Dec 08, 2022 |
| Title |
Heat Shock Protein Family A Member 1 Promotes Intracellular Amplification of Hepatitis B Virus Covalently Closed Circular DNA |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Hepatitis B virus (HBV) contains a partially double-stranded relaxed circular DNA (rcDNA) genome that is converted into a covalently closed circular DNA (cccDNA) in the nucleus of infected hepatocyte by cellular DNA repair machinery. cccDNA associates with nucleosomes to form a minichromosome that transcribes RNA to support the expression of viral proteins and reverse transcriptional replication of viral DNA. In addition to the de novo synthesis from incoming virion rcDNA, cccDNA can also been synthesized from rcDNA in the progeny nucleocapsids in the cytoplasm of infected hepatocytes via the intracellular amplification pathway. In our efforts to identify cellular DNA repair proteins required for cccDNA synthesis by a chemogenetic screen, we found that B02, a small molecular inhibitor of DNA homologous recombination repair protein RAD51, significantly enhanced the synthesis of cccDNA via intracellular amplification pathway in human hepatoma cells. Ironically, neither siRNA knockdown of RAD51 expression nor treatment with another structurally distinct RAD51 inhibitor or activator altered cccDNA amplification. However, further mechanistic studies revealed that B02 treatment significantly elevated the levels of multiple heat shock protein mRNA and siRNA knockdown of HSPA1A expression or treatment with HSPA1 inhibitors significantly attenuated B02 enhancement of cccDNA amplification. Moreover, B02 enhanced cccDNA amplification was efficiently inhibited by compounds that selectively inhibit DNA polymerase α or topoisomerase II, the enzymes required for cccDNA intracellular amplification. Our results thus indicate that B02 treatment induces a heat shock protein-mediated cellular response that positively regulates the conversion of rcDNA into cccDNA via the authentic intracellular amplification pathway
|
| |
|
| Overall design |
mRNA from control or B02 treated HepAD38 cells are sequenced and analyzed in three biological replicates
|
| |
|
| Contributor(s) |
Tang L, An P, Zhao Q, Winkler CA, Chang J, Guo J |
| Citation(s) |
36519896 |
| Submission date |
Jul 27, 2022 |
| Last update date |
Mar 09, 2023 |
| Contact name |
Ju-Tao Guo |
| E-mail(s) |
ju-tao.guo@bblumberg.org
|
| Phone |
2674321281
|
| Organization name |
Baruch S Blumberg Institute
|
| Street address |
3805 Old easton road
|
| City |
Doylestown |
| State/province |
PA |
| ZIP/Postal code |
18902 |
| Country |
USA |
| |
|
| Platforms (1) |
|
| Samples (6)
|
| GSM6402666 |
HepAD38 mRNA, B02 (20 uM), 7h, rep1 [s16] |
| GSM6402667 |
HepAD38 mRNA, B02 (20 uM), 7h, rep2 [s17] |
| GSM6402668 |
HepAD38 mRNA, B02 (20 uM), 7h, rep3 [s18] |
|
| Relations |
| BioProject |
PRJNA862739 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE209863_RPKMCountFile_Rsem_GEO.txt.gz |
255.1 Kb |
(ftp)(http) |
TXT |
| GSE209863_RawCountFile_Rsem_GEO.txt.gz |
833.2 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
|
|
|
|
 |
Less...
More...