Restricted activity
Epidermodysplasia verruciformis (EV) is a rare, autosomal recessive disorder that is associated with an unusually high susceptibility to infection with a specific set of human papilloma virus (HPV) genotypes (known as EV HPV). Most EV cases are caused by a mutation in the EVER1 or EVER2 genes, which encode endoplasmic reticulum membrane proteins. Lazarczyk et al. were interested in how these two proteins control EV HPV infection. Using yeast two-hybrid screening, pull-down assays and immunoprecipitation, the authors found that EVER1 and EVER2 form a complex with the zinc transporter ZnT-1, and further work showed that in keratinocytes EVER2 and ZnT-1 regulate the intracellular distribution of zinc, thereby controlling its entry into the nucleus. To analyse the connection between the EVER proteins, ZnT-1 and EV HPVs, immunoprecipitation assays involving early proteins from cutaneous and genital HPV genotypes (that is, genotypes that are not associated with EV) were carried out. The E5 protein from HPV16 was shown to bind to EVER1, EVER2 and ZnT-1 and inhibit their downregulation. The authors conclude that the lack of an E5 open-reading frame could account for the host restriction of EV HPVs. J. Exp. Med.
