Single-nucleotide variants in human CD81 influence hepatitis C virus infection of hepatoma cells.
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Authors
Alberione, María PíaMoeller, Rebecca
Kirui, Jared
Ginkel, Corinne
Doepke, Mandy
Ströh, Luisa J
Machtens, Jan-Philipp
Pietschmann, Thomas
Gerold, Gisa
Issue Date
2020-04-22
Metadata
Show full item recordAbstract
An estimated number of 71 million people are living with chronic hepatitis C virus (HCV) infection worldwide and 400,000 annual deaths are related to the infection. HCV entry into the hepatocytes is complex and involves several host factors. The tetraspanin human CD81 (hCD81) is one of the four essential entry factors and is composed of one large extracellular loop, one small extracellular loop, four transmembrane domains, one intracellular loop and two intracellular tails. The large extracellular loop interacts with the E2 glycoprotein of HCV. Regions outside the large extracellular loop (backbone) of hCD81 have a critical role in post-binding entry steps and determine susceptibility of hepatocytes to HCV. Here, we investigated the effect of five non-synonymous single-nucleotide variants in the backbone of hCD81 on HCV susceptibility. We generated cell lines that stably express the hCD81 variants and infected the cells using HCV pseudoparticles and cell culture-derived HCV. Our results show that all the tested hCD81 variants support HCV pseudoparticle entry with similar efficiency as wild-type hCD81. In contrast, variants A54V, V211M and M220I are less supportive to cell culture-derived HCV infection. This altered susceptibility is HCV genotype dependent and specifically affected the cell entry step. Our findings identify three hCD81 genetic variants that are impaired in their function as HCV host factors for specific viral genotypes. This study provides additional evidence that genetic host variation contributes to inter-individual differences in HCV infection and outcome.Citation
Med Microbiol Immunol. 2020 Aug;209(4):499-514. doi: 10.1007/s00430-020-00675-1. Epub 2020 Apr 22.Affiliation
TWINCORE, Zentrum für experimentelle und klinische Infektionsforschung GmbH,Feodor-Lynen Str. 7, 30625 Hannover, Germany.Publisher
SpringerPubMed ID
32322956Type
ArticleLanguage
enEISSN
1432-1831ae974a485f413a2113503eed53cd6c53
10.1007/s00430-020-00675-1
Scopus Count
The following license files are associated with this item:
- Creative Commons
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