title: A Non-enveloped Virus Hijacks Host Disaggregation Machinery to Translocate across the Endoplasmic Reticulum Membrane.
abstract: Mammalian cytosolic Hsp110 family, in concert with the Hsc70:J-protein complex, functions as a disaggregation machinery to rectify protein misfolding problems. Here we uncover a novel role of this machinery in driving membrane translocation during viral entry. The non-enveloped virus SV40 penetrates the endoplasmic reticulum (ER) membrane to reach the cytosol, a critical infection step. Combining biochemical, cell-based, and imaging approaches, we find that the Hsp110 family member Hsp105 associates with the ER membrane J-protein B14. Here Hsp105 cooperates with Hsc70 and extracts the membrane-penetrating SV40 into the cytosol, potentially by disassembling the membrane-embedded virus. Hence the energy provided by the Hsc70-dependent Hsp105 disaggregation machinery can be harnessed to catalyze a membrane translocation event.
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Madhu Sudhan
authors.initials: MS
authors.lastname: Ravindran
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Parikshit
authors.initials: P
authors.lastname: Bagchi
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
authors.forename: Billy
authors.initials: B
authors.lastname: Tsai
mesh_terms: D001692:Biological Transport / Q000502:physiology; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000821:virology*; D050883:HSC70 Heat-Shock Proteins / Q000378:metabolism; D050957:HSP110 Heat-Shock Proteins / Q000378:metabolism; D006790:Host-Parasite Interactions / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D027601:Polyomavirus Infections / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013539:Simian virus 40 / Q000472:pathogenicity*; D014162:Transfection; D014412:Tumor Virus Infections / Q000378:metabolism*
chemical_list: D050883:HSC70 Heat-Shock Proteins; D050957:HSP110 Heat-Shock Proteins; C494371:HSPA8 protein, human