Cutaneous human papillomavirus (HPV) types from the beta genus are ubiquitously distributed throughout the human body and may be part of the commensal flora. The association of beta-HPVs and the development of cutaneous squamous cell carcinomas (cSCC) were initially reported in patients with the rare genetic disorder Epidermodysplasia verruciformis (EV). About half of EV patients harbor mutations within the TMC6 or TMC8 genes which encode EVER1 and EVER2 proteins, respectively. It was recently suggested that among the general population EVER1/2 may act as a restriction factor to beta-HPV infections. It was also shown that EVER proteins form a complex with the zinc transporter-1 protein (ZnT-1) in keratinocytes controlling intracellular zinc concentration, consequently affecting the activity of zinc-modulated transcription factors (TFs), such as AP-1 family members. However, the exact mechanism underlying these findings is yet to be fully elucidated. To further investigate this issue, we propose to study the underling mechanisms by which EVER 1/2 restrict the beta-HPV life cycle in human keratinocytes. We aim to evaluate the transcriptional activity of beta1-HPV-5, beta2-HPV-38 and beta3-HPV-49 in parental and EVER1/2-depleted cells. Moreover, we will estimate the effect of UV irradiation and the role of the AP-1 complex in this context. Expanding this knowledge will contribute to better understand the biological proprieties of beta-HPVs and the pathogenesis of their associated diseases.
News published in Agência FAPESP Newsletter about the scholarship: