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Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB
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2018 (English)In: PLoS Pathogens, ISSN 1553-7366, E-ISSN 1553-7374, Vol. 14, no 7, article id e1007111Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2018. Vol. 14, no 7, article id e1007111
National Category
Microbiology in the medical area
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URN: urn:nbn:se:umu:diva-150844DOI: 10.1371/journal.ppat.1007111ISI: 000440351300009PubMedID: 30024968OAI: oai:DiVA.org:umu-150844DiVA, id: diva2:1244250
Available from: 2018-08-31 Created: 2018-08-31 Last updated: 2018-08-31Bibliographically approved

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Gerold, Gisa

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VirologyWallenberg Centre for Molecular Medicine at Umeå University (WCMM)
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