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Ganglioside-dependent cell attachment and endocytosis of murine polyomavirus-like particles

Alicia E Smith1, Hauke Lilie, Ari Helenius

  • 1Institute of Biochemistry, Swiss Federal Institute of Technology-Zurich, CH-8093, Zurich, Switzerland.

FEBS Letters
|December 4, 2003
PubMed

Insights

Mouse polyomavirus-like particles (PyVLP) bind to cells via gangliosides, a type of glycolipid. Restoring gangliosides to deficient cells re-established PyVLP attachment and uptake, confirming their role in viral entry.

Area of Science:

  • Virology
  • Cell Biology
  • Glycobiology

Background:

  • Murine polyomavirus (Py) infection is associated with cellular targets involving alpha2,3-linked sialic acids.
  • Understanding the precise molecular mechanisms of PyVLP interaction with host cells is crucial for viral pathogenesis research.

Purpose of the Study:

  • To investigate the role of gangliosides in the binding and cellular uptake of mouse polyomavirus-like particles (PyVLP).
  • To elucidate the specific cellular components mediating PyVLP attachment and entry into host cells.

Main Methods:

  • Treatment of fibroblast 3T6 cells with sialidase and protease to assess PyVLP binding.
  • Utilizing the ganglioside-deficient GM95 murine cell line to evaluate PyVLP binding and entry.
  • Restoration of gangliosides (G(M1), G(D1a), G(T1b)) to GM95 cells and subsequent assessment of PyVLP interaction.

Main Results:

  • Sialidase treatment significantly reduced PyVLP binding to 3T6 cells, while protease treatment had a moderate effect.
  • PyVLP binding and entry were diminished in ganglioside-deficient GM95 cells compared to control cells.
  • Addition of specific gangliosides to GM95 cells restored PyVLP binding and cellular uptake.

Conclusions:

  • Gangliosides, particularly G(M1), G(D1a), and G(T1b), are key mediators of PyVLP cell attachment.
  • Gangliosides play a significant role in the endocytosis process of PyVLP into host cells.
  • These findings identify gangliosides as critical cellular receptors for murine polyomavirus-like particles.

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