TY - JOUR
T1 - The human CIB1-EVER1-EVER2 complex governs keratinocyte-intrinsic immunity to β-papillomaviruses
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 G.
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
PY - 2018/1/1
Y1 - 2018/1/1
N2 - 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.
AB - 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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U2 - 10.1084/jem.20170308
DO - 10.1084/jem.20170308
M3 - Article
C2 - 30068544
AN - SCOPUS:85055867068
VL - 215
SP - 2289
EP - 2310
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 9
ER -