Genetic cause for epidermodysplasia verruciformis identified

Researchers have identified a potential explanation why some people with the rare skin condition epidermodysplasia verruciformis (EV) develop flat warts from the beta subtype of the human papilloma virus (β-HPV).

In the paper, published in Journal of Experimental Medicine (Aug. 1, 2018, online ahead of print), the authors noted that patients with EV sometimes have a mutation that results in a shortage of the protein CIB1. Investigators also observed that individuals with CIB1 deficiency have symptoms identical to those with mutations to EVER1 or EVER2, two genes previously linked to EV. They also noted that patients with EVER1 or EVER2 mutations have very low levels of CIB1, suggesting that the three proteins interact.

In patients with EV, β-HPV infects keratinocytes and spurs abnormal proliferation. The researchers concluded that the three proteins EVER1, EVER2, and CIB1 form a protein unit that, if working correctly, protects the skin cells from β-HPV. If part of that protein unit is compromised, β-HPV is able to replicate.

In a press release, the paper’s senior author Dr. Jean-Laurent Casanova said that β-HPV do not produce the two proteins E5 and E8, which other HPV strains do, and can cause common warts.

Dr. Casanova is a professor at St. Giles Laboratory of Human Genetics of Infectious Diseases, and senior attending physician at the Rockefeller University in New York city, and a visiting professor at the Necker Hospital for Sick Children, Paris Descartes University in Paris.

Individuals with EV are vulnerable to ß-HPVs because their own genetic irregularities nullify those of the viruses, Dr. Casanova suggested in the release. That is, the viruses can compensate for their missing proteins because the corresponding human defense mechanism is awry.

“When people have mutations in CIB1, EVER1 or EVER2, the ß-HPVs can promote the growth of keratinocytes—and can form warts and cancer—because there’s nothing to stop them, even though they are intrinsically defective, lacking E5 and E8” he said.