title: The agnoprotein of polyomavirus JC is released by infected cells: evidence for its cellular uptake by uninfected neighboring cells.
abstract: Poliomavirus JC replicates in glial cells in the brain, and causes the fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). PML is usually seen in patients with underlying immunocompromised conditions, notably among AIDS patients and those on chronic immunosuppressive regimens. The late leader sequence of JC virus contains an open reading frame encoding a small regulatory protein called agnoprotein. Agnoprotein contributes to progressive viral infection by playing significant roles in viral replication cycle. Here, we demonstrate that agnoprotein can be detected in cell-free fractions of glial cultures infected with JCV, transfected with expression plasmids or transduced with an adenovirus expression system. We also provide evidence that extracellular agnoprotein can be taken up by uninfected neighboring cells. These studies have revealed a novel phenomenon of agnoprotein during the viral life cycle with a potential of developing diagnostic and therapeutic interventions.
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, 3500 North Broad Street, 7th Floor, Philadelphia, PA 19140 USA.
authors.forename: Onder
authors.initials: O
authors.lastname: Otlu
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, 3500 North Broad Street, 7th Floor, Philadelphia, PA 19140 USA.
authors.forename: Francesca Isabella
authors.initials: FI
authors.lastname: De Simone
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, 3500 North Broad Street, 7th Floor, Philadelphia, PA 19140 USA.
authors.forename: Yolanda-Lopez
authors.initials: YL
authors.lastname: Otalora
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, 3500 North Broad Street, 7th Floor, Philadelphia, PA 19140 USA.
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, 3500 North Broad Street, 7th Floor, Philadelphia, PA 19140 USA. Electronic address: isariyer@temple.edu.
authors.forename: Ilker Kudret
authors.initials: IK
authors.lastname: Sariyer
mesh_terms: D000256:Adenoviridae; D045744:Cell Line, Tumor; D002474:Cell-Free System; D055354:Exosomes; D006801:Humans; D007577:JC Virus / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication / Q000502:physiology; D000086082:Viroporin Proteins
chemical_list: D054334:Viral Regulatory and Accessory Proteins; C042559:agnoprotein, polyomavirus; D000086082:Viroporin Proteins
keywords: Agnoprotein; Biomarker; JC virus; Release; Secretion; Uptake; Viral pathogenesis