Gangliosides are receptors for murine polyoma virus and SV40.
Polyoma virus (Py) and simian virus 40 (SV40) travel from the plasma membrane to the endoplasmic reticulum (ER) from where they enter the cytosol and then the nucleus to initiate infection. Here we demonstrate that specific gangliosides can serve as plasma membrane receptors for these viruses, GD1a and GT1b for Py and GM1 for SV40. Binding and flotation assays were used to show that addition of these gangliosides to phospholipid vesicles allowed specific binding of the respective viruses. The crystal structure of polyoma VP1 with a sialic acid-containing oligosaccharide was used to derive a model of how the two terminal sugars (sialic acid-alpha2,3-galactose) in one branch of GD1a and GT1b are recognized by the virus. A rat cell line deficient in ganglioside synthesis is poorly infectible by polyoma and SV40, but addition of the appropriate gangliosides greatly facilitates virus uptake, transport to the ER and infection. Lipid binding sites for polyoma are shown to be present in rough ER membranes, suggesting that the virus travel with the ganglioside(s) from the plasma membranes to the ER.
Tsai
Billy
B
Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
Gilbert
Joanna M
JM
Stehle
Thilo
T
Lencer
Wayne
W
Benjamin
Thomas L
TL
Rapoport
Tom A
TA
D000818:Animals; D036022:Capsid Proteins / Q000737:chemistry / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000821:virology; D004721:Endoplasmic Reticulum / Q000821:virology; D005677:G(M1) Ganglioside / Q000737:chemistry / Q000502:physiology; D005732:Gangliosides / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D046911:Macromolecular Substances; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D011120:Polyomavirus / Q000472:pathogenicity / Q000502:physiology*; D051381:Rats; D011991:Receptors, Virus / Q000737:chemistry / Q000502:physiology*; D013539:Simian virus 40 / Q000472:pathogenicity / Q000502:physiology*
D036022:Capsid Proteins; D005732:Gangliosides; D046911:Macromolecular Substances; D011991:Receptors, Virus; C062481:VP1 protein, polyomavirus; C021298:ganglioside, GD1a; C033851:ganglioside, GD1b; D005677:G(M1) Ganglioside