Role of the cytosolic domain of occludin in trafficking and HCV infection 1 Running Title: OCLN C-terminus and HCV entry 2 - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Traffic Année : 2019

Role of the cytosolic domain of occludin in trafficking and HCV infection 1 Running Title: OCLN C-terminus and HCV entry 2

Résumé

Synopsis 11 The importance of the C-terminal part of OCLN for HCV infection was assessed by a 12 serial deletion approach. The characterization of OCLN mutants revealed that the 13 first 18 residues of the C-terminal cytosolic tail constitute the minimal region required 14 for HCV infection in non-polarized and polarized hepatocyte, despite a loss of TJ 15 localization. Among these 18 residues, I279 and W281 were crucial for cell surface 16 expression of OCLN mutant and modulated its ability to mediate HCV infection. 17 18 Abstract 19 The role of the tight-junction (TJ) protein occludin (OCLN) in hepatitis C virus (HCV) 20 entry remains elusive. Here, we investigated the OCLN C-terminal cytosolic domain 21 in HCV infection. We expressed a series of C-terminal deletion mutants in Huh-7 22 cells KO for OCLN and characterized their functionality in HCV infection and 23 trafficking. Deleting the OCLN cytosolic domain led to protein instability and 24 intracellular retention. The first 15 residues (OCLN-C15 mutant) of the cytosolic 25 domain were sufficient for OCLN stability, but led to its accumulation in the trans 26 Golgi network (TGN) due to a deficient cell surface export after synthesis. In contrast, 27 OCLN-C18 mutant, containing the first 18 residues of the cytosolic domain, was 28 expressed at the cell surface and could mediate HCV infection. Point mutations in the 29 context of C18 showed that I279 and W281 are crucial residues for cell surface 30 expression of OCLN-C18. However, in the context of full-length OCLN, mutation of 31 these residues only partially affected infection and cell surface localization. 32 Importantly, the characterization of OCLN-C18 in human polarized hepatocytes 33

Domaines

Virologie
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Dates et versions

hal-02992396 , version 1 (06-11-2020)

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  • HAL Id : hal-02992396 , version 1

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Muriel Lavie, Lydia Linna, Rehab I Moustafa, Sandrine Belouzard, Masayoshi Fukasawa, et al.. Role of the cytosolic domain of occludin in trafficking and HCV infection 1 Running Title: OCLN C-terminus and HCV entry 2. Traffic, 2019. ⟨hal-02992396⟩
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