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Abl family tyrosine kinases regulate sialylated ganglioside receptors for polyomavirus

Alyson I Swimm1, William Bornmann, Mengxi Jiang

  • 1Department of Pathology and Laboratory Medicine, Emory University, Whitehead Research Bldg. 144, 615 Michael St., Atlanta, GA 30322, USA.

Journal of Virology
|February 26, 2010
PubMed

Insights

Abl family tyrosine kinases regulate polyomavirus infection by controlling cell surface gangliosides. Inhibiting these kinases reduces viral receptors, impacting viral attachment and replication.

Area of Science:

  • Virology
  • Cell Biology
  • Biochemistry

Background:

  • Sialylated lipids function as cellular receptors for polyomaviruses.
  • Polyomaviruses are associated with various diseases, including kidney transplant rejection.

Purpose of the Study:

  • To investigate the role of Abl family tyrosine kinases in polyomavirus replication.
  • To elucidate the mechanism by which Abl family kinases influence viral attachment.

Main Methods:

  • Utilized pharmacological inhibitors targeting Abl family kinases.
  • Employed cell lines derived from knockout mice lacking specific Abl family kinases.
  • Assessed ganglioside levels and viral binding under different kinase activity conditions.

Main Results:

  • Abl family tyrosine kinases are essential for mouse polyomavirus and BK virus replication.
  • Reduced Abl family kinase activity leads to decreased cell surface gangliosides, which are receptors for mouse polyomavirus.
  • Inhibiting sialidase activity can restore virion binding even without Abl family kinase activity.

Conclusions:

  • Abl family kinases modulate polyomavirus susceptibility by regulating ganglioside levels.
  • These kinases inhibit host cell sialidase activity, thereby reducing ganglioside turnover in the plasma membrane.
  • Targeting Abl family kinases represents a potential strategy for controlling polyomavirus infections.

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