Temporal gating of nuclear import: How Merkel cell polyomavirus exploits the cell cycle for nuclear entry

Merkel cell polyomavirus (MCPyV) is a small, DNA tumor virus that is causally linked to an aggressive form of human skin cancer called Merkel cell carcinoma. MCPyV is the only polyomavirus definitively shown to cause cancer in humans, yet little is known about how it establishes infection in target cells. In this study, we report an unconventional mechanism by which MCPyV enters the host cell nucleus, where viral genome replication occurs. We demonstrate that, unlike other known polyomaviruses, MCPyV does not require the nuclear pore complex during entry. Instead, it takes advantage of cell cycle-dependent nuclear envelope breakdown to deliver its genetic material into the nucleus. We further show that the VP1 major capsid protein is sufficient to facilitate this process. Overall, our findings reveal a novel mechanism of polyomavirus nuclear entry and provide insight into the diverse mechanisms that these viruses use to cause infection.