Claudin-6 and Occludin Natural Variants Found in a Patient Highly Exposed but Not Infected with Hepatitis C Virus (HCV) Do Not Confer HCV Resistance In Vitro

Autor: Fénéant, Lucie, Ghosn, Jade, Fouquet, Baptiste, Helle, François, Belouzard, Sandrine, Vausselin, Thibaut, Séron, Karin, Delfraissy, Jean-François, Dubuisson, Jean, Misrahi, Micheline, Cocquerel, Laurence
Přispěvatelé: Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Infection à VIH, réservoirs, diversité génétique et résistance aux antirétroviraux (ARV) (EA 7327), Université Paris Descartes - Paris 5 (UPD5), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Amiens-Picardie, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Sud - Paris 11 (UP11), This work was supported by the French National Agency for Research on AIDS and Viral Hepatitis (ANRS) (grants ANRS AO-2008-1 and ANRS AO 2013-2). L. F. and T. V. were supported by a fellowship from the French Ministry of Research. L. F. was also supported by a fellowship from the ANRS. S. B. was supported by a Marie Curie International Reintegration Grant (PIRG-GA-2009-256300), We thank Anne Françoise Batto, Véronique Descamps and Sophana Ung for their technical assistance. We thank the BioImaging Center Lille Facility for access to equipment. nk the BioImaging Center Lille Facility for access to equipment., Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: PLoS ONE
PLoS ONE, Public Library of Science, 2015, 10 (11), pp.e0142539. ⟨10.1371/journal.pone.0142539⟩
PLoS ONE, 2015, 10 (11), pp.e0142539. ⟨10.1371/journal.pone.0142539⟩
PLoS ONE, Vol 10, Iss 11, p e0142539 (2015)
ISSN: 1932-6203
Popis: International audience; The clinical course of Hepatitis C Virus (HCV) infection is highly variable between infected individual hosts: up to 80% of acutely HCV infected patients develop a chronic infection while 20% clear infection spontaneously. Spontaneous clearance of HCV infection can be predicted by several factors, including symptomatic acute infection, favorable IFNL3 polymorphisms and gender. In our study, we explored the possibility that variants in HCV cell entry factors might be involved in resistance to HCV infection. In a same case patient highly exposed but not infected by HCV, we previously identified one mutation in claudin-6 (CLDN6) and a rare variant in occludin (OCLN), two tight junction proteins involved in HCV entry into hepatocytes. Here, we conducted an extensive functional study to characterize the ability of these two natural variants to prevent HCV entry. We used lentiviral vectors to express Wildtype or mutated CLDN6 and OCLN in different cell lines and primary human hepatocytes. HCV infection was then investigated using cell culture produced HCV particles (HCVcc) as well as HCV pseudoparticles (HCVpp) expressing envelope proteins from different genotypes. Our results show that variants of CLDN6 and OCLN expressed separately or in combination did not affect HCV infection nor cell-to-cell transmission. Hence, our study highlights the complexity of HCV resistance mechanisms supporting the fact that this process probably not primarily involves HCV entry factors and that other unknown host factors may be implicated.
Databáze: OpenAIRE
Externí odkaz: