PXD019285

PXD019285 is an original dataset announced via ProteomeXchange.

Title	Interferon-induced degradation of the hepatitis B virus persistence form, cccDNA, depends on ISG20
Description	Hepatitis B virus (HBV) persists by depositing a covalently closed circular DNA (cccDNA) in the nucleus of infected cells that cannot be targeted by available antivirals. Cytokine treatments can diminish HBV cccDNA via APOBEC3-mediated deamination. Here we show that overexpression of APOBEC3A alone, however, was not sufficient to reduce cccDNA in HBV-infected cells. This required addition of interferon indicating that cccDNA degradation requires an additional, interferon-stimulated gene (ISG). Transcriptome analyses identified ISG20 as the only type I and II interferon-induced, nucleus-resident protein with annotated nuclease activity. ISG20 expression was detected in human livers in acute, self-limiting but not in chronic hepatitis B. ISG20 depletion abolished the interferon-induced loss of cccDNA, and co-expression of ISG20 and APOBEC3A was sufficient to diminish cccDNA. In conclusion, non-cytolytic HBV cccDNA decline requires induction of a deaminase and nuclease. Our findings highlight that ISGs cooperate for their antiviral function and this cooperativity may be explored for therapeutic targeting.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:21:22.732.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Urban
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-18 22:03:47	ID requested
1	2021-04-22 13:29:38	announced
⏵ 2	2024-10-22 05:21:23	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: ISG20, APOBEC3A, HBV, interferon-gamma, cccDNA, chronic hepatitis B, interferon-alpha

Andreas Pichlmair
contact affiliation	Institute of Virology, Technical University Munich
contact email	andreas.pichlmair@tum.de
lab head
Christian Urban
contact affiliation	Institute of Virology, Technical University Munich
contact email	c.urban@tum.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD019285
     1. Label: PRIDE project
     2. Name: Interferon-induced degradation of the hepatitis B virus persistence form, cccDNA, depends on ISG20