CD81 Receptor Regions outside the Large Extracellular Loop Determine Hepatitis C Virus Entry into Hepatoma Cells.
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Khan, Abdul G
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AbstractHepatitis C virus (HCV) enters human hepatocytes using four essential entry factors, one of which is human CD81 (hCD81). The tetraspanin hCD81 contains a large extracellular loop (LEL), which interacts with the E2 glycoprotein of HCV. The role of the non-LEL regions of hCD81 (intracellular tails, four transmembrane domains, small extracellular loop and intracellular loop) is poorly understood. Here, we studied the contribution of these domains to HCV susceptibility of hepatoma cells by generating chimeras of related tetraspanins with the hCD81 LEL. Our results show that non-LEL regions in addition to the LEL determine susceptibility of cells to HCV. While closely related tetraspanins (X. tropicalis CD81 and D. rerio CD81) functionally complement hCD81 non-LEL regions, distantly related tetraspanins (C. elegans TSP9 amd D. melanogaster TSP96F) do not and tetraspanins with intermediate homology (hCD9) show an intermediate phenotype. Tetraspanin homology and susceptibility to HCV correlate positively. For some chimeras, infectivity correlates with surface expression. In contrast, the hCD9 chimera is fully surface expressed, binds HCV E2 glycoprotein but is impaired in HCV receptor function. We demonstrate that a cholesterol-coordinating glutamate residue in CD81, which hCD9 lacks, promotes HCV infection. This work highlights the hCD81 non-LEL regions as additional HCV susceptibility-determining factors.
CitationCD81 Receptor Regions outside the Large Extracellular Loop Determine Hepatitis C Virus Entry into Hepatoma Cells. 2018, 10 (4) Viruses
AffiliationTWINCORE, Zentrum für experimentelle und klinischeInfektionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
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- The small extracellular loop of CD81 is necessary for optimal surface expression of the large loop, a putative HCV receptor.
- Authors: Masciopinto F, Campagnoli S, Abrignani S, Uematsu Y, Pileri P
- Issue date: 2001 Nov 28
- Mechanism of Structural Tuning of the Hepatitis C Virus Human Cellular Receptor CD81 Large Extracellular Loop.
- Authors: Cunha ES, Sfriso P, Rojas AL, Roversi P, Hospital A, Orozco M, Abrescia NGA
- Issue date: 2017 Jan 3
- Interaction of hepatitis C virus envelope glycoprotein E2 with the large extracellular loop of tupaia CD81.
- Authors: Tian ZF, Shen H, Fu XH, Chen YC, Blum HE, Baumert TF, Zhao XP
- Issue date: 2009 Jan 14
- Binding of hepatitis C virus E2 glycoprotein to CD81 does not correlate with species permissiveness to infection.
- Authors: Meola A, Sbardellati A, Bruni Ercole B, Cerretani M, Pezzanera M, Ceccacci A, Vitelli A, Levy S, Nicosia A, Traboni C, McKeating J, Scarselli E
- Issue date: 2000 Jul
- An intramolecular bond at cluster of differentiation 81 ectodomain is important for hepatitis C virus entry.
- Authors: Yang W, Zhang M, Chi X, Liu X, Qin B, Cui S
- Issue date: 2015 Oct