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Bunz, M.* ; Eisele, M.* ; Hu, D.* ; Ritter, M.* ; Kammerloher, J. ; Lampl, S. ; Schindler, M.*

CD81 suppresses NF-κB signaling and is downregulated in hepatitis C virus expressing cells.

Front. Cell. Infect. Microbiol. 14:1338606 (2024)
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The tetraspanin CD81 is one of the main entry receptors for Hepatitis C virus, which is a major causative agent to develop liver cirrhosis and hepatocellular carcinoma (HCC). Here, we identify CD81 as one of few surface proteins that are downregulated in HCV expressing hepatoma cells, discovering a functional role of CD81 beyond mediating HCV entry. CD81 was downregulated at the mRNA level in hepatoma cells that replicate HCV. Kinetics of HCV expression were increased in CD81-knockout cells and accompanied by enhanced cellular growth. Furthermore, loss of CD81 compensated for inhibition of pro-survival TBK1-signaling in HCV expressing cells. Analysis of functional phenotypes that could be associated with pro-survival signaling revealed that CD81 is a negative regulator of NF-κB. Interaction of the NF-κB subunits p50 and p65 was increased in cells lacking CD81. Similarly, we witnessed an overall increase in the total levels of phosphorylated and cellular p65 upon CD81-knockout in hepatoma cells. Finally, translocation of p65 in CD81-negative hepatoma cells was markedly induced upon stimulation with TNFα or PMA. Altogether, CD81 emerges as a regulator of pro-survival NF-κB signaling. Considering the important and established role of NF-κB for HCV replication and tumorigenesis, the downregulation of CD81 by HCV and the associated increase in NF-κB signaling might be relevant for viral persistence and chronic infection.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Cd81 ; Hcc ; Nf-κb ; Hepatitis C Virus ; Hepatocellular Carcinoma ; Tetraspanin; Nuclear-factor; Hepatocellular-carcinoma; Superinfection Exclusion; Protein-kinase; Surface Cd4; Core; Activation; Receptor; Liver; Interferon
ISSN (print) / ISBN 2235-2988
e-ISSN 2235-2988
Journal Frontiers in Cellular and Infection Microbiology
Quellenangaben Volume: 14, Issue: , Pages: , Article Number: 1338606 Supplement: ,
Publisher Frontiers
Publishing Place Lausanne
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)
Grants University Hospital Tubingen, Medical Faculty
DFG German Research Foundation