Simian Virus 40 depends on ER protein folding and quality control factors for entry into host cells
(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.
(Less)
- author
- Schelhaas, Mario ; Malmström, Johan LU ; Pelkmans, Lucas ; Haugstetter, Johannes ; Ellgaard, Lars ; Grünewald, Kay and Helenius, Ari
- publishing date
- 2007-11-02
- 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
-
- scopus:35548992416
- pmid:17981119
- 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
- 2024-10-14 12:35:08
@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}}, }