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

Sarah Jill De Jong, Amandine Créquer, Irina Matos, David Hum, Vignesh Gunasekharan, Lazaro Lorenzo, Fabienne Jabot-Hanin, Elias Imahorn, Andres A. Arias, Hassan Vahidnezhad, Leila Youssefian, Janet Markle, Etienne Patin, Aurelia D'Amico, Claire Q.F. Wang, Florian Full, Armin Ensser, Tina M. Leisner, Leslie V. Parise, Matthieu Bouaziz & 17 others Nataly Portilla Maya, Xavier Rueda Cadena, Bayaki Saka, Amir Hossein Saeidian, Nessa Aghazadeh, Sirous Zeinali, Peter Itin, James G. Krueger, Lou Laimins, Laurent Abel, Elaine Fuchs, Jouni Uitto, Jose Luis Franco, Bettina Burger, Gérard Orth, Emmanuelle Jouanguy, Jean Laurent Casanova

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Pages (from-to)2289-2310
Number of pages22
JournalJournal of Experimental Medicine
Volume215
Issue number9
DOIs
StatePublished - Jan 1 2018
Externally publishedYes

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Calcium-Binding Proteins
Keratinocytes
Integrins
Immunity
Epidermodysplasia Verruciformis
Proteins
human CIB1 protein
Protein Deficiency
Skin
Mutation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

De Jong, S. J., Créquer, A., Matos, I., Hum, D., Gunasekharan, V., Lorenzo, L., ... Casanova, J. L. (2018). The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to β-papillomaviruses. Journal of Experimental Medicine, 215(9), 2289-2310. https://doi.org/10.1084/jem.20170308

The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to β-papillomaviruses. / De Jong, Sarah Jill; Créquer, Amandine; Matos, Irina; Hum, David; Gunasekharan, Vignesh; Lorenzo, Lazaro; Jabot-Hanin, Fabienne; Imahorn, Elias; Arias, Andres A.; Vahidnezhad, Hassan; Youssefian, Leila; Markle, Janet; Patin, Etienne; D'Amico, Aurelia; Wang, Claire Q.F.; Full, Florian; Ensser, Armin; Leisner, Tina M.; Parise, Leslie V.; Bouaziz, Matthieu; Maya, Nataly Portilla; Cadena, Xavier Rueda; Saka, Bayaki; Saeidian, Amir Hossein; Aghazadeh, Nessa; Zeinali, Sirous; Itin, Peter; Krueger, James G.; Laimins, Lou; Abel, Laurent; Fuchs, Elaine; Uitto, Jouni; Franco, Jose Luis; Burger, Bettina; Orth, Gérard; Jouanguy, Emmanuelle; Casanova, Jean Laurent.

In: Journal of Experimental Medicine, Vol. 215, No. 9, 01.01.2018, p. 2289-2310.

Research output: Contribution to journalArticle

De Jong, SJ, Créquer, A, Matos, I, Hum, D, Gunasekharan, V, Lorenzo, L, Jabot-Hanin, F, Imahorn, E, Arias, AA, Vahidnezhad, H, Youssefian, L, Markle, J, Patin, E, D'Amico, A, Wang, CQF, Full, F, Ensser, A, Leisner, TM, Parise, LV, Bouaziz, M, Maya, NP, Cadena, XR, Saka, B, Saeidian, AH, Aghazadeh, N, Zeinali, S, Itin, P, Krueger, JG, Laimins, L, Abel, L, Fuchs, E, Uitto, J, Franco, JL, Burger, B, Orth, G, Jouanguy, E & Casanova, JL 2018, 'The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to β-papillomaviruses', Journal of Experimental Medicine, vol. 215, no. 9, pp. 2289-2310. https://doi.org/10.1084/jem.20170308
De Jong, Sarah Jill ; Créquer, Amandine ; Matos, Irina ; Hum, David ; Gunasekharan, Vignesh ; Lorenzo, Lazaro ; Jabot-Hanin, Fabienne ; Imahorn, Elias ; Arias, Andres A. ; Vahidnezhad, Hassan ; Youssefian, Leila ; Markle, Janet ; Patin, Etienne ; D'Amico, Aurelia ; Wang, Claire Q.F. ; Full, Florian ; Ensser, Armin ; Leisner, Tina M. ; Parise, Leslie V. ; Bouaziz, Matthieu ; Maya, Nataly Portilla ; Cadena, Xavier Rueda ; Saka, Bayaki ; Saeidian, Amir Hossein ; Aghazadeh, Nessa ; Zeinali, Sirous ; Itin, Peter ; Krueger, James G. ; Laimins, Lou ; Abel, Laurent ; Fuchs, Elaine ; Uitto, Jouni ; Franco, Jose Luis ; Burger, Bettina ; Orth, Gérard ; Jouanguy, Emmanuelle ; Casanova, Jean Laurent. / The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to β-papillomaviruses. In: Journal of Experimental Medicine. 2018 ; Vol. 215, No. 9. pp. 2289-2310.
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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 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.",
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AU - De Jong, Sarah Jill

AU - Créquer, Amandine

AU - Matos, Irina

AU - Hum, David

AU - Gunasekharan, Vignesh

AU - Lorenzo, Lazaro

AU - Jabot-Hanin, Fabienne

AU - Imahorn, Elias

AU - Arias, Andres A.

AU - Vahidnezhad, Hassan

AU - Youssefian, Leila

AU - Markle, Janet

AU - Patin, Etienne

AU - D'Amico, Aurelia

AU - Wang, Claire Q.F.

AU - Full, Florian

AU - Ensser, Armin

AU - Leisner, Tina M.

AU - Parise, Leslie V.

AU - Bouaziz, Matthieu

AU - Maya, Nataly Portilla

AU - Cadena, Xavier Rueda

AU - Saka, Bayaki

AU - Saeidian, Amir Hossein

AU - Aghazadeh, Nessa

AU - Zeinali, Sirous

AU - Itin, Peter

AU - Krueger, James G.

AU - Laimins, Lou

AU - Abel, Laurent

AU - Fuchs, Elaine

AU - Uitto, Jouni

AU - Franco, Jose Luis

AU - Burger, Bettina

AU - Orth, Gérard

AU - Jouanguy, Emmanuelle

AU - Casanova, Jean Laurent

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