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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 orcid ; 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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publishing date
type
Contribution to journal
publication status
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
  • pmid:17981119
  • 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
2024-04-14 17:20:25
@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}},
  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}},
  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}},
  doi          = {{10.1016/j.cell.2007.09.038}},
  volume       = {{131}},
  year         = {{2007}},
}