The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to beta-papillomaviruses
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 (2018)
Publication Type: Journal article
Publication year: 2018
Journal
Book Volume: 215
Pages Range: 2289-2310
Journal Issue: 9
DOI: 10.1084/jem.20170308
Abstract
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.
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Involved external institutions
Rockefeller University
United States (USA) (US)
University of North Carolina at Chapel Hill
United States (USA) (US)
Universitätsspital Basel
Switzerland (CH)
Universidad de Antioquía (UDEA)
Colombia (CO)
Hôpital Necker-Enfants malades
France (FR)
Fundación Universitaria de Ciencias de la Salud (FUCS)
Colombia (CO)
Thomas Jefferson University
United States (USA) (US)
Northwestern University
United States (USA) (US)
University of Lomé
Togo (TG)
Institut Pasteur
France (FR)
Tehran University of Medical Sciences (TUMS) / دانشگاه علوم پزشکی تهران
Iran, Islamic Republic of (IR)
National Cancer Institute (NCI)
United States (USA) (US)
Pasteur Institute of Iran (PII)
Iran, Islamic Republic of (IR)
United States (USA) (US)
University of North Carolina at Chapel Hill
United States (USA) (US)
Universitätsspital Basel
Switzerland (CH)
Universidad de Antioquía (UDEA)
Colombia (CO)
Hôpital Necker-Enfants malades
France (FR)
Fundación Universitaria de Ciencias de la Salud (FUCS)
Colombia (CO)
Thomas Jefferson University
United States (USA) (US)
Northwestern University
United States (USA) (US)
University of Lomé
Togo (TG)
Institut Pasteur
France (FR)
Tehran University of Medical Sciences (TUMS) / دانشگاه علوم پزشکی تهران
Iran, Islamic Republic of (IR)
National Cancer Institute (NCI)
United States (USA) (US)
Pasteur Institute of Iran (PII)
Iran, Islamic Republic of (IR)
How to cite
APA:
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. https://dx.doi.org/10.1084/jem.20170308
MLA:
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.
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