Roles of Lipid and Protein Receptors in Regulating Polyomavirus Infection.

[摘要] The non-enveloped murine polyomavirus (Py) binds to receptors on the cell surface to gain entry into host cells. The virus then traffics to the endoplasmic reticulum (ER) where it penetrates the membrane and enters the cytosol, finally reaching the nucleus to cause infection. How Py is transported from the plasma membrane to the ER, however, is not clear. The sialic acid-galactose containing gangsliosides GD1a and GT1b have been reported to be the functional receptors for Py to stimulate Py infection in host cells. Many glycoproteins, which also contain terminal sialic acid-galactose moiety, can in principle engage Py to be Py’s receptors. However, how these glycolipid and glycoprotein receptors guide Py intracellular transport and regulate Py infection are poorly understood. We show that GD1a is the functional entry receptor for Py. GD1a binds to Py on the plasma membrane, and the GD1a-Py complex is internalized and transported to the endolysosomes where the low pH triggers a conformational change that promotes the subsequent ER-to-cytosol membrane penetration of Py. GD1a then sorts Py from the endolysosomes to the ER, leading Py to the infectious pathway. By contrast, glycoproteins act as decoy receptors. They compete with GD1a on the cell surface and interact with Py, guiding Py to the endolysosomes where the virus is trapped and infection is restricted. Therefore, glycolipids and glycoproteins, two major constituents of the plasma membrane, act in opposing manners to control Py infection.

[发布机构] University of Michigan

[效力级别] Ganglioside

[关键词] Polyomavirus;Ganglioside;Lipid and Protein Receptors;Molecular;Cellular and Developmental Biology;Science;Cell and Developmental Biology