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Single-nucleotide v...
Single-nucleotide variants in human CD81 influence hepatitis C virus infection of hepatoma cells
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Alberione, Maria Pia (author)
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Moeller, Rebecca (author)
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Kirui, Jared (author)
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Ginkel, Corinne (author)
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Doepke, Mandy (author)
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Stroeh, Luisa J. (author)
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Machtens, Jan-Philipp (author)
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Pietschmann, Thomas (author)
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- Gerold, Gisa, 1979- (author)
- Umeå universitet,Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM),Avdelningen för virologi,Institute for Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, Hannover, Germany
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(creator_code:org_t)
- 2020-04-22
- 2020
- English.
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In: Medical Microbiology and Immmunology. - : Springer. - 0300-8584 .- 1432-1831. ; 209:4, s. 499-514
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
Keyword
- Hepatitis C virus
- HCV
- Hepatocyte
- Tetraspanin
- CD81
- Receptor
- Single-nucleotide variant
- Entry
- Genetic variant
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Alberione, Maria ...
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Moeller, Rebecca
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Kirui, Jared
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Ginkel, Corinne
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Doepke, Mandy
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Stroeh, Luisa J.
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show more...
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Machtens, Jan-Ph ...
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Pietschmann, Tho ...
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Gerold, Gisa, 19 ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Infectious Medic ...
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Medical Microbio ...
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Umeå University