TY - JOUR
T1 - Simian Virus 40 depends on ER protein folding and quality control factors for entry into host cells.
AU - Schelhaas, Mario
AU - Malmström, Johan
AU - Pelkmans, Lucas
AU - Haugstetter, Johannes
AU - Ellgaard, Lars
AU - Grünewald, Kay
AU - Helenius, Ari
N1 - Keywords: Cysteine; Disulfides; Endoplasmic Reticulum; Hela Cells; Humans; Isomerism; Polyomavirus Infections; Protein Disulfide-Isomerase; Protein Folding; Protein Processing, Post-Translational; Protein Structure, Quaternary; Simian virus 40; Sulfhydryl Compounds; Tumor Virus Infections; Viral Proteins; Virion; Virus Internalization
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
U2 - 10.1016/j.cell.2007.09.038
DO - 10.1016/j.cell.2007.09.038
M3 - Journal article
C2 - 17981119
SN - 0092-8674
VL - 131
SP - 516
EP - 529
JO - Cell
JF - Cell
IS - 3
ER -