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Zhao, L. ; Chen, F. ; Quitt, O. ; Festag, M. ; Ringelhan, M.* ; Wisskirchen, K. ; Festag, J. ; Yakovleva, L.* ; Sureau, C.* ; Bohne, F. ; Aichler, M. ; Bruss, V. ; Shevtsov, M.* ; van de Klundert, M. ; Momburg, F.* ; Möhl, B.S. ; Protzer, U.

Hepatitis B virus envelope proteins can serve as therapeutic targets embedded in the host cell plasma membrane.

Cell. Microbiol. 23:e13399 (2021)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Hepatitis B virus (HBV) infection is a major health threat causing 880,000 deaths each year. Available therapies control viral replication, but do not cure HBV leaving patients at risk to develop hepatocellular carcinoma. Here we show that HBV envelope proteins (HBs) - besides their integration into endosomal membranes - become embedded in the plasma membrane where they can be targeted by redirected T-cells. HBs was detected on the surface of HBV-infected cells, in livers of mice replicating HBV and in HBV-induced hepatocellular carcinoma. Staining with HBs-specific recombinant antibody MoMab recognizing a conformational epitope indicated that membrane-associated HBs remains correctly folded in HBV-replicating cells in cell culture and in livers of HBV-transgenic mice in vivo. MoMab coated onto superparamagnetic iron oxide nanoparticles allowed to detect membrane-associated HBs after HBV infection by electron microscopy in distinct stretches of the hepatocyte plasma membrane. Last not least we demonstrate that HBs located to the cell surface allows therapeutic targeting of HBV-positive cells by T-cells either engrafted with a chimeric antigen receptor or redirected by bispecific, T-cell engager antibodies. This article is protected by copyright. All rights reserved.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Antiviral Therapy ; Hbsag ; T-cell Therapy ; Envelope Proteins ; Plasma Membrane; Iron-oxide Nanoparticles; Surface-antigen; Hepatocellular-carcinoma; Transmembrane Domains; Replication; Polypeptide; Secretion; Binding; Hbsag; Identification
ISSN (print) / ISBN 1462-5814
e-ISSN 1462-5822
Zeitschrift Cellular Microbiology
Quellenangaben Band: 23, Heft: 12, Seiten: , Artikelnummer: e13399 Supplement: ,
Verlag Wiley
Verlagsort 111 River St, Hoboken 07030-5774, Nj Usa
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
Research Unit Analytical Pathology (AAP)
Förderungen Ministry of Science and Higher Education of The Russian Federation