The human CIB1–EVER1–EVER2 complex governs keratinocyte-intrinsic immunity to β-papillomaviruses

Autor: Matthieu Bouaziz, Sirous Zeinali, Vignesh Gunasekharan, Fabienne Jabot-Hanin, Sarah Jill De Jong, Peter Itin, Nessa Aghazadeh, Xavier Rueda Cadena, E. Imahorn, Aurelia D’Amico, Amandine Crequer, Irina Matos, Elaine Fuchs, Bettina Burger, Janet Markle, David Hum, Etienne Patin, Florian Full, Bayaki Saka, Amir Hossein Saeidian, Laurent Abel, James G. Krueger, Nataly Portilla Maya, Claire Q.F. Wang, Jouni Uitto, Emmanuelle Jouanguy, Leila Youssefian, Hassan Vahidnezhad, Armin Ensser, Andrés Augusto Arias, Leslie V. Parise, Tina M. Leisner, Jean-Laurent Casanova, Lou Laimins, Lazaro Lorenzo, Gérard Orth, José Luis Franco
Přispěvatelé: St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], Northwestern University [Evanston], Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), University of Basel (Unibas), Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Institut Pasteur d'Iran, Réseau International des Instituts Pasteur (RIIP), Sidney Kimmel Medical College [Philadelphia], Jefferson (Philadelphia University + Thomas Jefferson University), Tehran University of Medical Sciences (TUMS), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Fundación Universitaria de Ciencias de la Salud = University Foundation of Health Sciences [Bogotá, Colombia] (FUCS), Instituto Nacional de Cancerologia = National Cancer Institute [Bogotá], Université de Lomé [Togo], Kawsar Human Genetics Research Center, Kawsar Genomics and Biotech Cente, University Hospital Basel [Basel], Département de Virologie - Department of Virology, Institut Pasteur [Paris], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), The Laboratory of Human Genetics of Infectious Diseases is supported by grants from the National Institutes of Health (grant 5 R21 AI107508-02) and the French Cancer Institute (grant 2013-1-PL BIO-11-1). L.V. Parise and T.M. Leisner are supported by National Institutes of Health grant R41 CA200189. S.J. de Jong was supported by the German Research Foundation (Jo 1151-1), funds from the Women Science Fellowship program at The Rockefeller University, and the National Institutes of Health Clinical and Translational Science Award program (UL1 TR001866). J.L. Franco and A.A. Arias were supported by the Fundación Diana Garcia de Olarte FIP and Colciencias Programa de Intercambio de investigadores e innovadores Colombia-Francia (ECOS-NORD/COLCIENCIAS/MEN/ICETEX, 619-2013 and Colciencias contract 713-2016 code 111574455633)., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)
Rok vydání: 2018
Předmět:
Zdroj: Journal of Experimental Medicine
Journal of Experimental Medicine, Rockefeller University Press, 2018, 215 (9), pp.2289-2310. ⟨10.1084/jem.20170308⟩
Journal of Experimental Medicine, 2018, 215 (9), pp.2289-2310. ⟨10.1084/jem.20170308⟩
ISSN: 1540-9538
0022-1007
Popis: International audience; Patients with epidermodysplasia verruciformis (EV) and biallelic null mutations of TMC6 (encoding EVER1) or TMC8 (EVER2) are selectively prone to disseminated skin lesions due to keratinocyte-tropic human β-papillomaviruses (β-HPVs), which lack E5 and E8. We describe EV patients homozygous for null mutations of the CIB1 gene encoding calcium- and integrin-binding protein-1 (CIB1). CIB1 is strongly expressed in the skin and cultured keratinocytes of controls but not in those of patients. CIB1 forms a complex with EVER1 and EVER2, and CIB1 proteins are not expressed in EVER1- or EVER2-deficient cells. The known functions of EVER1 and EVER2 in human keratinocytes are not dependent on CIB1, and CIB1 deficiency does not impair keratinocyte adhesion or migration. In keratinocytes, the CIB1 protein interacts with the HPV E5 and E8 proteins encoded by α-HPV16 and γ-HPV4, respectively, suggesting that this protein acts as a restriction factor against HPVs. Collectively, these findings suggest that the disruption of CIB1-EVER1-EVER2-dependent keratinocyte-intrinsic immunity underlies the selective susceptibility to β-HPVs of EV patients.
Databáze: OpenAIRE
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