title: Role of a nuclear localization signal on the minor capsid proteins VP2 and VP3 in BKPyV nuclear entry.
abstract: BK Polyomavirus (BKPyV) is a ubiquitous nonenveloped human virus that can cause severe disease in immunocompromised populations. After internalization into renal proximal tubule epithelial cells, BKPyV traffics through the ER and enters the cytosol. However, it is unclear how the virus enters the nucleus. In this study, we elucidate a role for the nuclear localization signal located on the minor capsid proteins VP2 and VP3 during infection. Site-directed mutagenesis of a single lysine in the basic region of the C-terminus of the minor capsid proteins abrogated their nuclear localization, and the analogous genomic mutation reduced infectivity. Additionally, through use of the inhibitor ivermectin and knockdown of importin β1, we found that the importin α/β pathway is involved during infection. Overall these data are the first to show the significance of the NLS of the BKPyV minor capsid proteins during infection in a natural host cell.
authors.affiliation: Cellular and Molecular Biology Program University of Michigan 1150W Medical Center Dr 5724 Medical Science Bldg II Ann Arbor, MI 48109.
authors.forename: Shauna M
authors.initials: SM
authors.lastname: Bennett
authors.affiliation: Doctoral Program in Cancer Biology Program University of Michigan 1150W Medical Center Dr 5724 Medical Science Bldg II Ann Arbor, MI 48109.
authors.forename: Linbo
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Microbiology and Immunology University of Michigan 1150W Medical Center Dr 5724 Medical Science Bldg II Ann Arbor, MI 48109.
authors.forename: Catherine
authors.initials: C
authors.lastname: Bosard
authors.affiliation: Cellular and Molecular Biology Program University of Michigan 1150W Medical Center Dr 5724 Medical Science Bldg II Ann Arbor, MI 48109; Doctoral Program in Cancer Biology Program University of Michigan 1150W Medical Center Dr 5724 Medical Science Bldg II Ann Arbor, MI 48109; Department of Microbiology and Immunology University of Michigan 1150W Medical Center Dr 5724 Medical Science Bldg II Ann Arbor, MI 48109. Electronic address: imperial@umich.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Imperiale
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001739:BK Virus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D055785:Gene Knockdown Techniques; D054884:Host-Pathogen Interactions; D006801:Humans; D007559:Ivermectin / Q000494:pharmacology; D007687:Kidney Tubules, Proximal / Q000821:virology; D008239:Lysine / Q000737:chemistry; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D019913:Nuclear Localization Signals / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D053586:Virus Internalization; D028961:beta Karyopherins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology
chemical_list: D036022:Capsid Proteins; C424166:KPNB1 protein, human; D019913:Nuclear Localization Signals; C442543:VP2 protein, Polyomavirus; D028961:beta Karyopherins; D007559:Ivermectin; D008239:Lysine
keywords: Intracellular virus trafficking; Nuclear entry; Polyomavirus