Simian Virus 40 Depends on ER Protein Folding and Quality Control Factors for Entry into Host Cells

• Published in: Cell 2007-11, Vol.131 (3), p.516-529
• Main Authors: Schelhaas, Mario, Malmström, Johan, Pelkmans, Lucas, Haugstetter, Johannes, Ellgaard, Lars, Grünewald, Kay, Helenius, Ari
• Format: Article
• Language: English
• Subjects: CELLBIO; Cysteine - metabolism; Disulfides - metabolism; Endoplasmic Reticulum - metabolism; HeLa Cells; Humans; Isomerism; Polyomavirus Infections - virology; Protein Disulfide-Isomerases - chemistry; Protein Disulfide-Isomerases - metabolism; Protein Folding; Protein Processing, Post-Translational; Protein Structure, Quaternary; PROTEINS; Simian virus 40; Simian virus 40 - physiology; Simian virus 40 - ultrastructure; Sulfhydryl Compounds - metabolism; Tumor Virus Infections - virology; Viral Proteins - metabolism; Virion - metabolism; Virion - ultrastructure; Virus Internalization
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2007.09.038

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.