EMC1-dependent stabilization drives membrane penetration of a partially destabilized non-enveloped virus

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Abstract

Destabilization of a non-enveloped virus generates a membrane transport-competent viral particle. Here we probe polyomavirus SV40 endoplasmic reticulum (ER)-to-cytosol membrane transport, a decisive infection step where destabilization initiates this non-enveloped virus for membrane penetration. We find that a member of the ER membrane protein complex (EMC) called EMC1 promotes SV40 ER membrane transport and infection. Surprisingly, EMC1 does so by using its predicted transmembrane residue D961 to bind to and stabilize the membrane-embedded partially destabilized SV40, thereby preventing premature viral disassembly. EMC1-dependent stabilization enables SV40 to engage a cytosolic extraction complex that ejects the virus into the cytosol. Thus EMC1 acts as a molecular chaperone, bracing the destabilized SV40 in a transport-competent state. Our findings reveal the novel principle that coordinated destabilization-stabilization drives membrane transport of a non-enveloped virus.

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Parikshit Bagchi

Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Takamasa Inoue

Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States

Competing interests
The authors declare that no competing interests exist.
Billy Tsai

Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States

For correspondence
btsai@umich.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2859-1415

Funding

National Institute of Allergy and Infectious Diseases (AI064296; GM113722)

Billy Tsai

University of Michigan Protein Folding Disease Initiative (University Funds)

Billy Tsai

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.