HPV: CIB1 is for EVER and EVER

Abstract

In this issue, de Jong et al. (https://doi.org/10.1084/jem.20170308) identify bi-allelic loss-of-expression, loss-of-function mutations of the calcium- and integrin-binding protein 1 (CIB1) gene as a new cause of epidermodysplasia verruciformis (EV) and demonstrate that the CIB1 interacts with the EVER1 and EVER2 proteins to form a complex involved in keratinocyte-intrinsic immune response to human β-papillomaviruses (β-HPVs).

Insight from Luigi D. Notarangelo.

From de Jong et al. (2018). (A) In the general population, the CIB1/EVER1/2 complex restricts the transcription of the minichromosome of β-HPV, leading to the absence of clinical manifestation. The proteins E5 and E8 expressed by the other cutaneous HPVs (α2-, α4-, γ-, and μ-HPVs) are able to antagonize the CIB1/EVER1/2 complex. However, additional restriction factors are probably contributing to the absence of HPV lesions in the vast majority of people. (B) In EV patients, the lack of CIB1/EVER1/2 permits the transcription of β-HPV minichromosome, which leads to the development of EV lesions on the skin. However, the probable presence of additional restriction factors against cutaneous HPVs other than β-HPVs accounts for their normal control, which does not differ from the general population.