title: Ganglioside GD1a restores infectibility to mouse cells lacking functional receptors for polyomavirus.
abstract: Recent investigations on the pathway of cell entry by polyomavirus (Py) and simian virus 40 (SV40) have defined specific gangliosides as functional receptors mediating virus binding and transport from the plasma membrane to the endoplasmic reticulum (B. Tsai et al., EMBO J. 22:4346-4355, 2003; Gilbert and Benjamin, in press). These studies were carried out with C6 rat glioma cells, a heterologous host chosen for its known deficiency in ganglioside biosynthesis. Here, a cell genetic approach was undertaken to identify components required for the early steps of infection using mouse cells as the natural host for Py. Receptor-negative (R-) mouse cells, screened based on resistance to Py infection, were shown to bind Py but failed to allow entry of the virus. R- cells were also found to be resistant to SV40. Infectibility was restored or enhanced by the addition of the same specific gangliosides found in earlier studies with C6 cells. In one R- line, overexpression of caveolin-1 also increased infectibility. These results support and extend findings on gangliosides in lipid rafts as functional receptors and mediators of internalization for Py and SV40.
authors.affiliation: Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Joanna
authors.initials: J
authors.lastname: Gilbert
authors.forename: Jean
authors.initials: J
authors.lastname: Dahl
authors.forename: Cathy
authors.initials: C
authors.lastname: Riney
authors.forename: John
authors.initials: J
authors.lastname: You
authors.forename: Cunqi
authors.initials: C
authors.lastname: Cui
authors.forename: Randall
authors.initials: R
authors.lastname: Holmes
authors.forename: Wayne
authors.initials: W
authors.lastname: Lencer
authors.forename: Thomas
authors.initials: T
authors.lastname: Benjamin
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D005732:Gangliosides / Q000378:metabolism*; D005910:Glioma; D051379:Mice; D041681:NIH 3T3 Cells; D011120:Polyomavirus / Q000472:pathogenicity*; D051381:Rats; D011991:Receptors, Virus / Q000378:metabolism*
chemical_list: D005732:Gangliosides; D011991:Receptors, Virus; C021298:ganglioside, GD1a