title: EMC1-dependent stabilization drives membrane penetration of a partially destabilized non-enveloped virus.
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.
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.
authors.forename: Parikshit
authors.initials: P
authors.lastname: Bagchi
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, United States.
authors.forename: Billy
authors.identifier: 0000-0003-2859-1415
authors.initials: B
authors.lastname: Tsai
mesh_terms: D000818:Animals; D001692:Biological Transport; D019556:COS Cells; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins; D011506:Proteins / Q000378:metabolism*; D013539:Simian virus 40 / Q000502:physiology*; D053586:Virus Internalization
chemical_list: C543592:EMC10 protein, human; D008565:Membrane Proteins; D011506:Proteins
keywords: cell biology; human; infectious disease; membrane transport; microbiology; protein stabilization; viral entry