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Related Experiment Video

Updated: Feb 12, 2026

siRNA Screening to Identify Ubiquitin and Ubiquitin-like System Regulators of Biological Pathways in Cultured Mammalian Cells
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Flavivirus internalization is regulated by a size-dependent endocytic pathway.

Brent A Hackett1, Sara Cherry2

  • 1Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104.

Proceedings of the National Academy of Sciences of the United States of America
|April 4, 2018
PubMed
Summary

Lymphocyte antigen 6 locus E (LY6E) aids flavivirus entry into cells. This protein is crucial for internalizing large particles like viruses and beads via clathrin-mediated endocytosis, forming tubules essential for uptake.

Keywords:
LY6Eendocytosisentryflavivirusvirus

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Area of Science:

  • Cell Biology
  • Virology
  • Molecular Biology

Background:

  • Flavivirus entry into host cells relies on clathrin-mediated endocytosis.
  • The specific host factors governing this process, especially for large viral particles, remain largely unknown.
  • Understanding these factors is crucial for developing antiviral strategies.

Purpose of the Study:

  • To identify host factors involved in flavivirus internalization.
  • To investigate the role of Lymphocyte antigen 6 locus E (LY6E) in flavivirus uptake.
  • To elucidate the mechanism by which LY6E facilitates the internalization of large cargo.

Main Methods:

  • Investigated the role of LY6E in the internalization of West Nile virus, Zika virus, and dengue virus.
  • Utilized transferrin and transferrin-coated beads to assess cargo size specificity.
  • Employed cell biological studies to observe LY6E-mediated tubule formation and its dependence on RNASEK and microtubules.
  • Screened microtubule end-binding proteins, including EB3, for their role in virus uptake.

Main Results:

  • LY6E was found to promote the internalization of multiple flaviviruses.
  • LY6E is selectively required for the uptake of large cargo, such as viruses and transferrin-coated beads, but not transferrin alone.
  • LY6E forms tubules dependent on RNASEK and microtubule assembly, which are essential for flavivirus uptake.
  • EB3 was identified as a microtubule end-binding protein that promotes virus uptake and LY6E tubule formation.

Conclusions:

  • LY6E plays a critical role in facilitating the clathrin-mediated endocytosis of flaviviruses and other large cargoes.
  • A specialized pathway involving LY6E, RNASEK, and microtubules is required for the uptake of large endocytic particles.
  • These findings offer insights into the distinct mechanisms governing the internalization of viral pathogens.