title: Caveolin- and clathrin-independent entry of BKPyV into primary human proximal tubule epithelial cells.
abstract: BK polyomavirus (BKPyV) is a human pathogen that causes polyomavirus-associated nephropathy and hemorrhagic cystitis in transplant patients. Gangliosides and caveolin proteins have previously been reported to be required for BKPyV infection in animal cell models. Recent studies from our lab and others, however, have indicated that the identity of the cells used for infection studies can greatly influence the behavior of the virus. We therefore wished to re-examine BKPyV entry in a physiologically relevant primary cell culture model, human renal proximal tubule epithelial cells. Using siRNA knockdowns, we interfered with expression of UDP-glucose ceramide glucosyltransferase (UGCG), and the endocytic vesicle coat proteins caveolin 1, caveolin 2, and clathrin heavy chain. The results demonstrate that while BKPyV does require gangliosides for efficient infection, it can enter its natural host cells via a caveolin- and clathrin-independent pathway. The results emphasize the importance of studying viruses in a relevant cell culture model.
authors.affiliation: Doctoral Program in Cancer Biology, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: linboz@umich.edu.
authors.forename: Linbo
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: marciano@umich.edu.
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Marciano
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: crrivet@umich.edu.
authors.forename: Courtney R
authors.initials: CR
authors.lastname: Rivet
authors.affiliation: Doctoral Program in Cancer Biology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: imperial@umich.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Imperiale
mesh_terms: D001739:BK Virus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D051242:Caveolin 1 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D051243:Caveolin 2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D033922:Clathrin Heavy Chains / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000821:virology; D005677:G(M1) Ganglioside / Q000494:pharmacology; D005732:Gangliosides / Q000494:pharmacology; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000821:virology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization / Q000187:drug effects; D000099237:UDP-Galactose Translocators
chemical_list: D051242:Caveolin 1; D051243:Caveolin 2; D033922:Clathrin Heavy Chains; D005677:G(M1) Ganglioside; D005732:Gangliosides; D035683:MicroRNAs; D009004:Monosaccharide Transport Proteins; D034741:RNA, Small Interfering; D000099237:UDP-Galactose Translocators; C495540:CAV1 protein, human; C033851:ganglioside, GD1b; C016481:trisialoganglioside GT1
keywords: BKPyV; Caveolin; Clathrin; Endocytosis; Entry; Ganglioside; UGCG