Hepatitis B virus envelope proteins can serve as therapeutic targets embedded in the host cell plasma membrane.
HBsAg
T-cell therapy
antiviral therapy
envelope proteins
plasma membrane
Journal
Cellular microbiology
ISSN: 1462-5822
Titre abrégé: Cell Microbiol
Pays: India
ID NLM: 100883691
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
revised:
21
10
2021
received:
25
04
2021
accepted:
22
10
2021
pubmed:
4
11
2021
medline:
14
1
2022
entrez:
3
11
2021
Statut:
ppublish
Résumé
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 recognising 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 but not least, we demonstrate that HBs located on the cell surface allow therapeutic targeting of HBV-positive cells by T-cells either engrafted with a chimeric antigen receptor or redirected by bispecific, T-cell engager antibodies. TAKE AWAYS: HBs become translocated to the plasma membrane. Novel, recombinant antibody confirmed proper conformation of HBs on the membrane. HBs provide an interesting target by T-cell-based, potentially curative therapies.
Substances chimiques
Hepatitis B Surface Antigens
0
Viral Envelope Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13399Subventions
Organisme : Deutsche Forschungsgemeinschaft
ID : TRR179 project number 2378635
Organisme : Deutsche Forschungsgemeinschaft
ID : TP18
Organisme : Deutsches Zentrum für Infektionsforschung
ID : DZIF Academy Maternity Leave Stipends TI 07.005
Organisme : Helmholtz-Gemeinschaft
ID : Helmholtz Validation Fund
Organisme : Russian Foundation for Basic Research
ID : 20-38-70039
Organisme : Ministry of Science and Higher Education of the Russian Federation
Informations de copyright
© 2021 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd.
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