title: Simian Virus 40 depends on ER protein folding and quality control factors for entry into host cells.
abstract: Cell entry of Simian Virus 40 (SV40) involves caveolar/lipid raft-mediated endocytosis, vesicular transport to the endoplasmic reticulum (ER), translocation into the cytosol, and import into the nucleus. We analyzed the effects of ER-associated processes and factors on infection and on isolated viruses and found that SV40 makes use of the thiol-disulfide oxidoreductases, ERp57 and PDI, as well as the retrotranslocation proteins Derlin-1 and Sel1L. ERp57 isomerizes specific interchain disulfides connecting the major capsid protein, VP1, to a crosslinked network of neighbors, thus uncoupling about 12 of 72 VP1 pentamers. Cryo-electron tomography indicated that loss of interchain disulfides coupled with calcium depletion induces selective dissociation of the 12 vertex pentamers, a step likely to mimic uncoating of the virus in the cytosol. Thus, the virus utilizes the protein folding machinery for initial uncoating before exploiting the ER-associated degradation machinery presumably to escape from the ER lumen into the cytosol.
authors.affiliation: Institute of Biochemistry, Schafmattstrasse 18, ETH Hoenggerberg, ETH Zurich, CH-8093, Zurich, Switzerland.
authors.forename: Mario
authors.initials: M
authors.lastname: Schelhaas
authors.forename: Johan
authors.initials: J
authors.lastname: Malmström
authors.forename: Lucas
authors.initials: L
authors.lastname: Pelkmans
authors.forename: Johannes
authors.initials: J
authors.lastname: Haugstetter
authors.forename: Lars
authors.initials: L
authors.lastname: Ellgaard
authors.forename: Kay
authors.initials: K
authors.lastname: Grünewald
authors.forename: Ari
authors.initials: A
authors.lastname: Helenius
mesh_terms: D003545:Cysteine / Q000378:metabolism; D004220:Disulfides / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007536:Isomerism; D027601:Polyomavirus Infections / Q000821:virology; D019704:Protein Disulfide-Isomerases / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D020836:Protein Structure, Quaternary; D013539:Simian virus 40 / Q000502:physiology* / Q000648:ultrastructure; D013438:Sulfhydryl Compounds / Q000378:metabolism; D014412:Tumor Virus Infections / Q000821:virology; D014764:Viral Proteins / Q000378:metabolism; D014771:Virion / Q000378:metabolism / Q000648:ultrastructure; D053586:Virus Internalization
chemical_list: D004220:Disulfides; D013438:Sulfhydryl Compounds; D014764:Viral Proteins; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human; D003545:Cysteine