title: Role of cell-type-specific endoplasmic reticulum-associated degradation in polyomavirus trafficking.
abstract: BK polyomavirus (BKPyV) is a widespread human pathogen that establishes a lifelong persistent infection and can cause severe disease in immunosuppressed patients. BKPyV is a nonenveloped DNA virus that must traffic through the endoplasmic reticulum (ER) for productive infection to occur; however, it is unknown how BKPyV exits the ER before nuclear entry. In this study, we elucidated the role of the ER-associated degradation (ERAD) pathway during BKPyV intracellular trafficking in renal proximal tubule epithelial (RPTE) cells, a natural host cell. Using proteasome and ERAD inhibitors, we showed that ERAD is required for productive entry. Altered trafficking and accumulation of uncoated viral intermediates were detected by fluorescence in situ hybridization and indirect immunofluorescence in the presence of an inhibitor. Additionally, we detected a change in localization of partially uncoated virus within the ER during proteasome inhibition, from a BiP-rich area to a calnexin-rich subregion, indicating that BKPyV accumulated in an ER subcompartment. Furthermore, inhibiting ERAD did not prevent entry of capsid protein VP1 into the cytosol from the ER. By comparing the cytosolic entry of the related polyomavirus simian virus 40 (SV40), we found that dependence on the ERAD pathway for cytosolic entry varied between the polyomaviruses and between different cell types, namely, immortalized CV-1 cells and primary RPTE cells.
authors.affiliation: Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
authors.forename: Shauna M
authors.initials: SM
authors.lastname: Bennett
authors.forename: Mengxi
authors.initials: M
authors.lastname: Jiang
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Imperiale
mesh_terms: D000818:Animals; D001739:BK Virus / Q000502:physiology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D060746:Endoplasmic Reticulum-Associated Degradation; D004847:Epithelial Cells / Q000821:virology; D006801:Humans; D021381:Protein Transport; D013539:Simian virus 40 / Q000502:physiology*; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D014764:Viral Proteins