Dataset Information

Identification of cellular protein interacting with HBV genome by protein mass spectrometry

ABSTRACT: : Hepatitis B virus (HBV) remains a major public health threat with more than 296 million people chronically infected worldwide at high risk to develop hepatocellular carcinoma. Current therapies are effective in suppressing HBV replication but rarely lead to cure. The fundamental limitation rests on the fact that current therapies do not affect the HBV covalently closed circular DNA (cccDNA), which serves as the template for viral transcription and replication and is highly stable in infected cells to ensure viral persistence. In this study, we aim to identify and elucidate the functional role of cccDNA-associated host factors using affinity purification and protein mass spectrometry in HBV-infected cells. HBV core protein (HBc) is associated with cccDNA. We used an anti-HBc antibody to pull down HBcAg-associated cccDNA complex in nuclear extract of HBV-infected HepG2-NTCP cells. By protein mass spectrometry, we identified many host proteins, including previously known proteins, that are associated with HBV cccDNA. Some of these proteins were functionally validated to play a role in HBV cccDNA activities.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Liver

DISEASE(S): Hepatitis B

SUBMITTER: David Anderson

LAB HEAD: T. Jake Liang

PROVIDER: PXD042733 | Pride | 2024-06-16

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	Chicken.fasta	Fasta
	UNIPROThuman032016.fasta	Fasta
	allSpectra.CID.FTMS.iso_0.apl	Other
	allSpectra.CID.FTMS.iso_1.apl	Other
	allSpectra.CID.FTMS.iso_2.apl	Other

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Publications

Nucleolin binds to and regulates transcription of hepatitis B virus covalently closed circular DNA minichromosome.

Xia Yuchen Y Cheng Xiaoming X Nilsson Tobias T Zhang Min M Zhao Gaihong G Inuzuka Tadashi T Teng Yan Y Li Yao Y Anderson D Eric DE Holdorf Meghan M Liang T Jake TJ

Proceedings of the National Academy of Sciences of the United States of America 20231128 49

Hepatitis B virus (HBV) remains a major public health threat with nearly 300 million people chronically infected worldwide who are at a high risk of developing hepatocellular carcinoma. Current therapies are effective in suppressing HBV replication but rarely lead to cure. Current therapies do not affect the HBV covalently closed circular DNA (cccDNA), which serves as the template for viral transcription and replication and is highly stable in infected cells to ensure viral persistence. In this ...[more]

PMID: 38015841

Similar Datasets

Project description:Chronic hepatitis B virus (HBV) infections remain a health burden affecting ~250 million people worldwide. Thus far, available interferon-alpha (IFNα)-based therapies have shown unsatisfactory cure rates, and alternative therapeutic molecules are still required. However, their development has been hampered because accessible cell models supporting relevant HBV replication and appropriate antiviral activity are lacking. Strategies that reverse epigenetic alterations offer a unique opportunity for cell reprogramming, which is valuable for restoring altered cellular functions in human cell lines. This work aimed to investigate the feasibility of converting HepG2 cells that stably overexpress the HBV entry receptor (sodium/taurocholate cotransporting polypeptide, NTCP) toward IFNα-responsive cells using epigenetic reprogramming. Herein, we showed that an epigenetic regimen with non-cytotoxic doses of the demethylating compound 5-azacytidine restored the anti-HBV action of IFNα in epigenetically reprogrammed HepG2-NTCP-C4 cells, named REP-HepG2-NTCP cells. Thus, a significant inhibition in HBV DNA levels was measured in REP-HepG2-NTCP cells after IFNα treatment. This inhibitory effect was associated with the enhancement of IFNα-mediated induction of critical interferon-stimulated genes (ISGs), which was limited in non-reprogrammed cells. In particular, our data indicated that re-expression of 2’-5’-oligoadenylate synthetase 1 (OAS1) and interferon regulatory factor 9 (IRF9) was the result of an epigenetically driven unmasking of these genes in reprogrammed cells. At last, we evaluated the therapeutic potential of the IFN analog CDM-3008 in REP-HepG2-NTCP cells and demonstrated the efficiency of this chemical compound in triggering ISG induction and HBV inhibition. In summary, this study shows that epigenetic reprogramming promotes the IFNα response in HBV-infected cells and is potentially attractive for cell-based experimental screening of IFN-like compounds.