A Non-enveloped Virus Hijacks Host Disaggregation Machinery to Translocate across the Endoplasmic Reticulum Membrane

PLoS Pathogens

Billy Tsai¹  Madhu Sudhan Ravindran¹  Takamasa Inoue¹  Parikshit Bagchi¹ 

[1] Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America

关键词: SV40;    Cytosol;    Small interfering RNAs;    Immunoblotting;    Virions;    Immunoprecipitation;    Transfection;    Polymerase chain reaction;   

DOI  :  10.1371/journal.ppat.1005086

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY