Journal Article

DKFZ-2026-02312

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Hepatitis B virus proteome analysis identifies apolipoprotein C1 facilitating particle production and virus entry.

Yang, S. (First author)DKFZ* ; Nebioglu, F. (First author)DKFZ* ; Pham, M. T. ; Lin, Y.-C. ; Pichlmair, A. ; Nkongolo, S. ; Scaturro, P. ; Urban, S. ; Seitz, S. ; Bartenschlager, R. (Last author)DKFZ*

2026
Wolters Kluwer Health [Alphen aan den Rijn]

Abstract: Antiviral therapies targeting hepatitis B virus (HBV) suppress viral replication, but rarely achieve functional cure. Understanding HBV-host cell interaction is crucial for developing novel therapeutic approaches. Here, we report host cell proteins associated with HBV virions and filamentous subviral particles (fSVPs) and characterize one host cell protein, apolipoprotein C1 (ApoC1), mechanistically.Highly purified HBV virions and fSVPs were obtained by sequential use of several biophysical methods. Particles were analyzed by mass spectrometry and associated proteins were evaluated phenotypically using an HBV infection model. The top hit, ApoC1 was characterized in detail.Alongside the established HBV-associated chaperones HSP90AB1 and HSC70, we identified several apolipoprotein-related factors associated with virions and fSVPs. RNAi-based phenotypic validation identified strongest effects for ApoC1, likely due to two complementary effects. First, ApoC1 depletion reduced intracellular cholesterol level impairing HBV infection and SVP production, which was compensated by exogenous cholesterol addition. Second, ApoC1 that is mainly enriched in high-density lipoprotein (HDL), associates with HBV virions and fSVPs and increases HBV infectivity. The same was found for hepatitis D virus (HDV), a satellite virus utilizing HBV envelopes. Supplementation of exogenous HDL enhanced infection via scavenger receptor class B type 1 (SR-B1), the natural HDL receptor. Consistently, inhibition of SR-B1 suppressed HBV and HDV infection.We established a method for obtaining highly purified HBV virions and fSVPs and identified the HDL component ApoC1 to associate with both particle types. ApoC1 promotes HBV and HDV infection most likely via SR-B1 and facilitates viral entry.

Keyword(s): HBV proteome ; hepatitis D virus (HDV) ; high-density lipoprotein (HDL) ; scavenger receptor class B type 1 (SR-B1) ; subviral particles (SVPs)

Note: #EA:D430#LA:D430# / epub

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Contributing Institute(s):

1. Virus-assoziierte Karzinogenese (D430)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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