PXD066477

PXD066477 is an original dataset announced via ProteomeXchange.

Title	IFI35 suppresses the transcription of hepatitis B virus cccDNA minichromosome via promoting HNF4α proteasomal degradation
Description	Hepatitis B virus (HBV) infection is a major health problem with hundreds of millions of people still chronically infected worldwide. Although it is known that cytokines can inhibit HBV replication in infected hepatocytes, much is still unknown about the underlying mechanisms or mediators. In this study, we systematically analyzed tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)induced proteins by proteomic analysis and identified interferon-inducible protein 35 (IFI35) as a novel host restriction factor for HBV replication. Overexpression of IFI35 suppressed HBV transcription, while its reduction showed the opposite effect. Mechanistically, IFI35 regulated the stability of hepatocyte nuclear factor 4α (HNF4α), which is essential for cccDNA transcription. IFI35 did not regulate the transcription of HNF4α but rather promoted its degradation. We found that IFI35 recruits tripartite motif-containing protein 21 (TRIM21), an E3 ubiquitin-protein ligase, for K48-linked ubiquitination of HNF4α. Results were further validated using patient-derived primary human hepatocytes (PHHs) and mouse model of HBV infection. Our results revealed that cytokines, especially IFN-γ, induced IFI35 in hepatocytes. IFI35 promoted the degradation of HNF4α via the TRIM21-mediated ubiquitination, which, in turn, leads to the suppression of cccDNA transcription and viral replication. Our findings demonstrate that IFI35-TRIM21-HNF4α axis may play a crucial role in TNF-α and IFN-γ induced suppression of HBV. Consequently, these results reveal a novel antiviral action of IFI35 against HBV. These findings may hold value in the development of alternative anti-HBV drugs.
HostingRepository	PRIDE
AnnounceDate	2026-08-24
AnnouncementXML	Submission_2026-08-23_16:56:41.698.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jaewon Oh
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-23 09:26:30	ID requested
⏵ 1	2026-08-23 16:56:42	announced

Kim N, Shin JJ, Oh JW, Won J, Lee AR, Dezhbord M, Park J, Lee KY, Kim DS, Kim KP, Kim KH, proteasomal degradation. J Biomed Sci, 33(1):(2026) [pubmed]

10.1186/s12929-026-01239-w;

submitter keyword: Human, HBV, Proteomics

Jae Won Oh
contact affiliation	Kyung Hee University
contact email	odinplate@naver.com
lab head
Jaewon Oh
contact affiliation	Kyung Hee University
contact email	odinplate@naver.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066477
     1. Label: PRIDE project
     2. Name: IFI35 suppresses the transcription of hepatitis B virus cccDNA minichromosome via promoting HNF4α proteasomal degradation