Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB

PLoS Pathogens
Janina BrueningGisa Gerold

Abstract

Hepatitis C virus (HCV) and the malaria parasite Plasmodium use the membrane protein CD81 to invade human liver cells. Here we mapped 33 host protein interactions of CD81 in primary human liver and hepatoma cells using high-resolution quantitative proteomics. In the CD81 protein network, we identified five proteins which are HCV entry factors or facilitators including epidermal growth factor receptor (EGFR). Notably, we discovered calpain-5 (CAPN5) and the ubiquitin ligase Casitas B-lineage lymphoma proto-oncogene B (CBLB) to form a complex with CD81 and support HCV entry. CAPN5 and CBLB were required for a post-binding and pre-replication step in the HCV life cycle. Knockout of CAPN5 and CBLB reduced susceptibility to all tested HCV genotypes, but not to other enveloped viruses such as vesicular stomatitis virus and human coronavirus. Furthermore, Plasmodium sporozoites relied on a distinct set of CD81 interaction partners for liver cell entry. Our findings reveal a comprehensive CD81 network in human liver cells and show that HCV and Plasmodium highjack selective CD81 interactions, including CAPN5 and CBLB for HCV, to invade cells.

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Citations

May 14, 2019·Viral Immunology·Tarak DhaouadiYousr Gorgi
Aug 21, 2019·Cold Spring Harbor Perspectives in Medicine·Gisa GeroldThomas Pietschmann
Jun 17, 2020·PLoS Pathogens·Huanle LuoTian Wang
Mar 22, 2020·International Journal of Molecular Sciences·Che C ColpittsMirjam B Zeisel
Mar 27, 2020·Scientific Reports·Jérôme FinkeThorsten Lang
Apr 24, 2020·Medical Microbiology and Immunology·María Pía AlberioneGisa Gerold
Jun 15, 2020·Medical Microbiology and Immunology·Jérôme FinkeThorsten Lang
Jun 26, 2020·Frontiers in Cardiovascular Medicine·Kikkie PoelsTom T P Seijkens
Sep 10, 2020·The Journal of Biological Chemistry·Machaela PalorJoe Grove
Jan 24, 2021·Immunologic Research·Yueqi ChenFang Liu
Feb 15, 2021·Molecular Metabolism·Ciro SalinnoHeiko Lickert
Jan 18, 2021·The Journal of Biological Chemistry·Machaela PalorJoe Grove
Apr 4, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Vimala BondadaJames W Geddes
Aug 10, 2021·World Journal of Gastroenterology : WJG·Hui-Chun LiShih-Yen Lo

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Methods Mentioned

BETA
co-immunoprecipitations
pull out
flow cytometry
co-IPs
co-IP
ubiquitination
fluorescence microscopy
Infection
transfection
interaction profiling

Software Mentioned

Cytoscape
Bioconductor package
IntAct
Image J
R
STRING
RNAither
GraphPad Prism
MaxQuant
FluoView

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