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

Journal article

Publication Details

Author(s): De Jong SJ, Crequer A, Matos I, Hum D, Gunasekharan V, Lorenzo L, Jabot-Hanin F, Imahorn E, Arias AA, Vahidnezhad H, Youssefian L, Markle JG, Patin E, D'Amico A, Wang CQF, Full F, Enßer A, Leisner TM, Parise LV, Bouaziz M, Portilla Maya N, Rueda Cadena X, Saka B, Saeidian AH, Aghazadeh N, Zeinali S, Itin P, Krueger JG, Laimins L, Abel L, Fuchs E, Uitto J, Luis Franco J, Burger B, Orth G, Jouanguy E, Casanova JL
Journal: Journal of Experimental Medicine
Publication year: 2018
Volume: 215
Journal issue: 9
Pages range: 2289-2310
ISSN: 0022-1007


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 beta-papillomaviruses (beta-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 alpha-HPV16 and gamma-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 beta-HPVs of EV patients.

FAU Authors / FAU Editors

Enßer, Armin Prof. Dr.
Medizinische Fakultät

External institutions with authors

Fundación Universitaria de Ciencias de la Salud (FUCS)
Hôpital Necker-Enfants malades
Institut Pasteur
National Cancer Institute (NCI)
Northwestern University
Pasteur Institute of Iran (PII)
Rockefeller University
Tehran University of Medical Sciences
Thomas Jefferson University
Universidad de Antioquía (UDEA)
Universitätsspital Basel
University of Lomé
University of North Carolina at Chapel Hill

How to cite

De Jong, S.J., Crequer, A., Matos, I., Hum, D., Gunasekharan, V., Lorenzo, L.,... Casanova, J.-L. (2018). The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to beta-papillomaviruses. Journal of Experimental Medicine, 215(9), 2289-2310.

De Jong, Sarah Jill, et al. "The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to beta-papillomaviruses." Journal of Experimental Medicine 215.9 (2018): 2289-2310.


Last updated on 2019-01-02 at 08:23