2008_The_CD81_Partner_EWI-2wint_Inhibits_Hepatitis_C_Virus_entry

2008_The_CD81_Partner_EWI-2wint_Inhibits_Hepatitis_C_Virus_entry

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The CD81 Partner EWI-2wint Inhibits Hepatitis C Virus Entry Vera Rocha-Perugini 1 . , Claire Montpellier 1 . , David Delgrange 1 , Czeslaw Wychowski 1 , Franc ¸ois Helle 1 , Andre ´ Pillez 1 , Herve ´ Drobecq 1 , Franc ¸ois Le Naour 3 , Ste ´phanie Charrin 3 , Shoshana Levy 2 , Eric Rubinstein 3 , Jean Dubuisson 1 * , Laurence Cocquerel 1,2 * 1 Institut de Biologie de Lille (UMR8161), CNRS, Universite ´s de Lille I et Lille II, Institut Pasteur de Lille, Lille, France, 2 Division of Oncology, Department of Medicine, Stanford University Medical Center, Stanford, California, United States of America, 3 INSERM-U602, Institut Andre ´-Lwoff, Universite ´ Paris XI, Ho ˆpital Paul Brousse, Villejuif, France Abstract Two to three percent of the world’s population is chronically infected with hepatitis C virus (HCV) and thus at risk of developing liver cancer. Although precise mechanisms regulating HCV entry into hepatic cells are still unknown, several cell surface proteins have been identified as entry factors for this virus. Among these molecules, the tetraspanin CD81 is essential for HCV entry. Here, we have identified a partner of CD81, EWI-2wint, which is expressed in several cell lines but not in hepatocytes. Ectopic expression of EWI-2wint in a hepatoma cell line susceptible to HCV infection blocked viral entry by inhibiting the interaction between the HCV envelope glycoproteins and CD81. This finding suggests that, in addition to the presence of specific entry factors in the hepatocytes, the lack of a specific inhibitor can contribute to the hepatotropism of HCV. This is the first example of a pathogen gaining entry into host cells that lack a specific inhibitory factor. Citation: Rocha-Perugini V, Montpellier C, Delgrange D, Wychowski C, Helle F, et al. (2008) The CD81 Partner EWI-2wint Inhibits Hepatitis C Virus Entry. PLoS ONE 3(4): e1866. doi:10.1371/journal.pone.0001866 Editor: Nina Papavasiliou, The Rockefeller University, United States of America Received August 9, 2007; Accepted February 18, 2008; Published April 2, 2008 Copyright: ß 2008 Rocha-Perugini et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was supported by the ‘‘Institut Fe ´de ´ratif de Recherche-142’’ (IFR142) and by grants from the CNRS and the « Agence Nationale de Recherches sur le Sida et les he ´patites virales » ANRS. V R-P was supported by a fellowship from the « Institut Pasteur de Lille/Re ´gion Nord Pas-de-Calais ». DD was supported by a fellowship from the ANRS. FH was supported by a fellowship from the French Ministry of Research. JD is an international scholar of the Howard Hughes Medical Institute.
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2008_The_CD81_Partner_EWI-2wint_Inhibits_Hepatitis_C_Virus_entry

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