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

Karen Wang1, Adrienne N Eady1, Isabel Amaya1

  • 1Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.

Plos Pathogens
|May 30, 2025
PubMed

Insights

Merkel cell polyomavirus (MCPyV), a skin cancer virus, enters host cell nuclei unconventionally. It bypasses nuclear pores by utilizing cell cycle-dependent nuclear envelope breakdown for infection.

Area of Science:

  • Virology
  • Oncology
  • Cell Biology

Background:

  • Merkel cell polyomavirus (MCPyV) is a DNA tumor virus linked to Merkel cell carcinoma, an aggressive human skin cancer.
  • MCPyV is the only polyomavirus proven to cause cancer in humans, but its infection mechanism remains poorly understood.

Purpose of the Study:

  • To elucidate the mechanism of MCPyV nuclear entry.
  • To investigate how MCPyV delivers its genetic material into the host cell nucleus for replication.

Main Methods:

  • Investigated MCPyV nuclear entry pathways in host cells.
  • Utilized cell cycle analysis to observe nuclear envelope dynamics during viral entry.
  • Assessed the role of the VP1 major capsid protein in nuclear import.

Main Results:

  • MCPyV enters the host cell nucleus without utilizing the nuclear pore complex.
  • Viral entry is facilitated by the breakdown of the nuclear envelope during the cell cycle.
  • The VP1 major capsid protein alone is sufficient to mediate this unconventional nuclear entry.

Conclusions:

  • MCPyV employs a novel, cell cycle-dependent mechanism for nuclear entry, distinct from other polyomaviruses.
  • This discovery provides new insights into viral infection strategies and polyomavirus diversity.
  • Understanding this pathway may offer new avenues for therapeutic interventions against MCPyV-associated cancers.

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