RT Journal Article
SR Electronic
T1 Hepatitis B virus envelope proteins can serve as therapeutic targets embedded in the host cell plasma membrane
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.21.423802
DO 10.1101/2020.12.21.423802
A1 Lili Zhao
A1 Fuwang Chen
A1 Oliver Quitt
A1 Marvin Festag
A1 Marc Ringelhan
A1 Karin Wisskirchen
A1 Julia Hasreiter
A1 Luidmila Yakovleva
A1 Camille Sureau
A1 Felix Bohne
A1 Michaela Aichler
A1 Volker Bruss
A1 Maxim Shevtsov
A1 Maarten van de Klundert
A1 Frank Momburg
A1 Britta S. Möhl
A1 Ulrike Protzer
YR 2020
UL http://biorxiv.org/content/early/2020/12/22/2020.12.21.423802.abstract
AB 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 confirmational 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 stretched 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.