The human CIB1–EVER1–EVER2 complex governs keratinocyte-intrinsic immunity to β-papillomaviruses
2 Rockefeller University [New York]
3 Northwestern University [Evanston]
4 Inserm U980 - Génétique Humaine des Maladies Infectieuses
5 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
6 Unibas - Université de Bâle = University of Basel = Basel Universität
7 Universidad de Antioquia = University of Antioquia [Medellín, Colombia]
8 Institut Pasteur d'Iran
9 Sidney Kimmel Medical College [Philadelphia]
10 TUMS - Tehran University of Medical Sciences
11 Génétique Evolutive Humaine - Human Evolutionary Genetics
12 C3BI - Centre de Bioinformatique, Biostatistique et Biologie Intégrative
13 FAU - Friedrich-Alexander Universität Erlangen-Nürnberg = University of Erlangen-Nuremberg
14 UNC-Chapel Hill - Université de Caroline du Nord à Chapel Hill = University of North Carolina [Chapel Hill]
15 FUCS - Fundación Universitaria de Ciencias de la Salud = University Foundation of Health Sciences [Bogotá, Colombia]
16 Instituto Nacional de Cancerologia = National Cancer Institute [Bogotá]
17 Université de Lomé [Togo]
18 Kawsar Human Genetics Research Center
19 University Hospital Basel [Basel]
20 Département de Virologie - Department of Virology
21 Hôpital Necker - Enfants Malades [AP-HP]
22 HHMI - Howard Hughes Medical Institute [New York]
- Fonction : Auteur
- PersonId : 798210
- ORCID : 0000-0001-5374-321X
- Fonction : Auteur
- PersonId : 795619
- ORCID : 0000-0003-1973-0911
- IdRef : 260708607
- Fonction : Auteur
- PersonId : 1517061
- IdHAL : lazaro-lorenzo
- ORCID : 0000-0001-6648-8684
- Fonction : Auteur
- PersonId : 179015
- IdHAL : etienne-patin
- ORCID : 0000-0002-9911-4459
- IdRef : 132614553
- Fonction : Auteur
- PersonId : 1479983
- IdRef : 17528234X
- Fonction : Auteur
- PersonId : 756190
- ORCID : 0000-0002-7358-9157
- IdRef : 224367455
- Fonction : Auteur correspondant
- PersonId : 955134
Connectez-vous pour contacter l'auteur
Résumé
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.
Domaines
| Origine | Fichiers éditeurs autorisés sur une archive ouverte |
|---|---|
| Licence |