title: Molecular interplay between T-Antigen and splicing factor, arginine/serine-rich 1 (SRSF1) controls JC virus gene expression in glial cells.
abstract: BACKGROUND
  Human polyomavirus JCV is the etiologic agent of progressive multifocal leukoencephalopathy (PML), a fatal demyelinating disease characterized by lytic infection of glial cells in the central nervous system. PML is seen primarily in immunosuppressed patients and is mainly classified as an AIDS-defining disease. In addition to structural capsid proteins, JCV encodes multiple regulatory proteins, including T-antigen and agnoprotein, which are required for functional lytic infection. Previous studies have suggested that molecular interaction between viral proteins and host factors play an important role in reactivation of JCV and progression of the viral life cycle in glial cells. Recently, serine/arginine rich splicing factor 1 (SRSF1), a cellular alternative splicing factor, was identified as a strong negative regulator of JCV in glial cells. SRSF1 inhibits JCV gene expression and viral replication by directly interacting with viral promoter sequences. Here, we have investigated possible impact of JCV regulatory proteins, T-antigen and agnoprotein, on SRSF1-mediated suppression of JCV gene expression in glial cells.
  
  
  RESULTS
  Reporter gene analysis has suggested that T-antigen rescues viral transcriptional suppression mediated by SRSF1. Further analyses have revealed that T-antigen promotes viral gene expression by suppressing SRSF1 gene transcription in glial cells. A subsequent ChIP analysis revealed that T-antigen associates with the promoter region of SRSF1 to induce the transcriptional suppression.
  
  
  CONCLUSIONS
  These findings have revealed a molecular interplay between cellular SRSF1 and viral T-antigen in controlling JCV gene expression, and may suggest a novel mechanism of JCV reactivation in patients who are at risk of developing PML.
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University Lewis Katz School of Medicine, 3500 North Broad Street, 7th Floor, Philadelphia, PA, 19140, USA. tub84653@temple.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Craigie
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University Lewis Katz School of Medicine, 3500 North Broad Street, 7th Floor, Philadelphia, PA, 19140, USA. tub67205@temple.edu.
authors.forename: Patrick
authors.initials: P
authors.lastname: Regan
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University Lewis Katz School of Medicine, 3500 North Broad Street, 7th Floor, Philadelphia, PA, 19140, USA. ylopez@temple.edu.
authors.forename: Yolanda-Lopez
authors.initials: YL
authors.lastname: Otalora
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University Lewis Katz School of Medicine, 3500 North Broad Street, 7th Floor, Philadelphia, PA, 19140, USA. isariyer@temple.edu.
authors.forename: Ilker Kudret
authors.initials: IK
authors.lastname: Sariyer
mesh_terms: D000957:Antigens, Viral, Tumor / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007577:JC Virus / Q000276:immunology* / Q000502:physiology*; D009457:Neuroglia / Q000276:immunology* / Q000821:virology*; D000068103:Serine-Arginine Splicing Factors / Q000378:metabolism*
chemical_list: D000957:Antigens, Viral, Tumor; C000595779:SRSF1 protein, human; D000068103:Serine-Arginine Splicing Factors