Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB.
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Authors
Bruening, JaninaLasswitz, Lisa
Banse, Pia
Kahl, Sina
Marinach, Carine
Vondran, Florian W
Kaderali, Lars
Silvie, Olivier
Pietschmann, Thomas
Meissner, Felix
Gerold, Gisa
Issue Date
2018-07-01
Metadata
Show full item recordAbstract
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.PubMed ID
30024968Type
ArticleISSN
1553-7374ae974a485f413a2113503eed53cd6c53
10.1371/journal.ppat.1007111
Scopus Count
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