EVERs keep zinc out of the nucleus by trapping zinc transporters (green) at the ER (red).

Zinc might strengthen our immune systems and fortify our bones, but it also helps a cancer-causing skin virus take hold, according to Lazarczyk et al. (page 35).

Most people harbor within their skin a human papillomavirus (HPV) subtype called HPV EV. Although this virus is usually harmless, certain infected individuals develop wart-like skin lesions that eventually grow into tumors. These rare, susceptible individuals have mutated versions of ER membrane proteins known as EVER1 and EVER2.

Lazarczyk et al. now show that normal versions of EVER proteins counter the virus by depriving the cell's nucleus of zinc—a known transcription booster. Zinc is shuttled into the nucleus by a transporter called ZnT-1. But the team found that EVERs bound and retained ZnT-1 at the ER, thus keeping the level of zinc in the nucleus low.

Cells containing mutated versions of EVERs had abnormally high levels of nuclear zinc, which activated proproliferation transcription factors, thus increasing the host cell's ability to seed tumors. Adding back functional EVERs reduced cellular proliferation. As the extra zinc also activated cellular transcription factors required for viral replication, EVERs might normally block viral replication as well.

Unlike HPV EV, the group found, other HPVs fought back against EVER proteins. One version that causes genital cancer, for instance, manufactured a protein that disrupted the EVER–ZnT-1 complex and freed zinc for nuclear entry.