Abl family tyrosine kinases regulate sialylated ganglioside receptors for polyomavirus.
Sialylated lipids serve as cellular receptors for polyomaviruses. Using pharmacological inhibitors and cell lines derived from knockout mice, we demonstrate that Abl family tyrosine kinases are required for replication of mouse polyomavirus and BK virus, a human polyomavirus associated with allograft failure following kidney transplantation. We show that decreasing Abl family kinase activity results in low levels of cell surface ganglioside receptors for mouse polyomavirus and that inhibition of sialidase activity promotes virion binding in the absence of Abl family kinase activity. These data provide evidence that Abl family kinases reduce ganglioside turnover in the plasma membrane by inhibiting host cell sialidase activity. Thus, Abl family kinases regulate the susceptibility of cells to polyomavirus infection by modulating gangliosides required for viral attachment.
Swimm
Alyson I
AI
Department of Pathology and Laboratory Medicine, Emory University, Whitehead Research Bldg. 144, 615 Michael St., Atlanta, GA 30322, USA.
Bornmann
William
W
Jiang
Mengxi
M
Imperiale
Michael J
MJ
Lukacher
Aron E
AE
Kalman
Daniel
D
D000818:Animals; D001739:BK Virus / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009439:Neuraminidase / Q000037:antagonists & inhibitors; D016374:Oncogene Proteins v-abl / Q000378:metabolism*; D011120:Polyomavirus / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000096:biosynthesis*; D053586:Virus Internalization
D016374:Oncogene Proteins v-abl; D011956:Receptors, Cell Surface; C034993:ganglioside receptor; D011505:Protein-Tyrosine Kinases; D009439:Neuraminidase