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

Research output: Contribution to journalArticle

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 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.

Details

Authors
  • Mario Schelhaas
  • Johan Malmström
  • Lucas Pelkmans
  • Johannes Haugstetter
  • Lars Ellgaard
  • Kay Grünewald
  • Ari Helenius
External organisations
  • ETH Zürich
Research areas and keywords

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
Original languageEnglish
Pages (from-to)516-29
Number of pages14
JournalCell
Volume131
Issue number3
Publication statusPublished - 2007 Nov 2
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes