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Simian Virus 40 depends on ER protein folding and quality control factors for entry into host cells

Schelhaas, Mario; Malmström, Johan LU ; Pelkmans, Lucas; Haugstetter, Johannes; Ellgaard, Lars; Grünewald, Kay and Helenius, Ari (2007) In Cell 131(3). p.29-516
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... (More)

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.

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published
keywords
Cysteine, Disulfides, Endoplasmic Reticulum, HeLa Cells, Humans, Isomerism, Polyomavirus Infections, Protein Disulfide-Isomerases, Protein Folding, Protein Processing, Post-Translational, Protein Structure, Quaternary, Simian virus 40, Sulfhydryl Compounds, Tumor Virus Infections, Viral Proteins, Virion, Virus Internalization, Journal Article, Research Support, Non-U.S. Gov't
in
Cell
volume
131
issue
3
pages
14 pages
publisher
Cell Press
external identifiers
  • scopus:35548992416
ISSN
0092-8674
DOI
10.1016/j.cell.2007.09.038
language
English
LU publication?
no
id
0de0715a-0530-4839-8ecb-ba527e02053f
date added to LUP
2017-09-04 17:21:37
date last changed
2017-10-22 05:35:35
@article{0de0715a-0530-4839-8ecb-ba527e02053f,
  abstract     = {<p>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.</p>},
  author       = {Schelhaas, Mario and Malmström, Johan and Pelkmans, Lucas and Haugstetter, Johannes and Ellgaard, Lars and Grünewald, Kay and Helenius, Ari},
  issn         = {0092-8674},
  keyword      = {Cysteine,Disulfides,Endoplasmic Reticulum,HeLa Cells,Humans,Isomerism,Polyomavirus Infections,Protein Disulfide-Isomerases,Protein Folding,Protein Processing, Post-Translational,Protein Structure, Quaternary,Simian virus 40,Sulfhydryl Compounds,Tumor Virus Infections,Viral Proteins,Virion,Virus Internalization,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {11},
  number       = {3},
  pages        = {29--516},
  publisher    = {Cell Press},
  series       = {Cell},
  title        = {Simian Virus 40 depends on ER protein folding and quality control factors for entry into host cells},
  url          = {http://dx.doi.org/10.1016/j.cell.2007.09.038},
  volume       = {131},
  year         = {2007},
}