title: Human polyoma JC virus minor capsid proteins, VP2 and VP3, enhance large T antigen binding to the origin of viral DNA replication: evidence for their involvement in regulation of the viral DNA replication.
abstract: JC virus (JCV) lytically infects the oligodendrocytes in the central nervous system in a subset of immunocompromized patients and causes the demyelinating disease, progressive multifocal leukoencephalopathy. JCV replicates and assembles into infectious virions in the nucleus. However, understanding the molecular mechanisms of its virion biogenesis remains elusive. In this report, we have attempted to shed more light on this process by investigating molecular interactions between large T antigen (LT-Ag), Hsp70 and minor capsid proteins, VP2/VP3. We demonstrated that Hsp70 interacts with VP2/VP3 and LT-Ag; and accumulates heavily in the nucleus of the infected cells. We also showed that VP2/VP3 associates with LT-Ag through their DNA binding domains resulting in enhancement in LT-Ag DNA binding to Ori and induction in viral DNA replication. Altogether, our results suggest that VP2/VP3 and Hsp70 actively participate in JCV DNA replication and may play critical roles in coupling of viral DNA replication to virion encapsidation.
authors.affiliation: Department of Neuroscience, Laboratory of Molecular Neurovirology, MERB-757, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, United States.
authors.forename: A Sami
authors.initials: AS
authors.lastname: Saribas
authors.affiliation: Department of Neuroscience, Laboratory of Molecular Neurovirology, MERB-757, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, United States.
authors.forename: Sarah
authors.initials: S
authors.lastname: Mun
authors.affiliation: Department of Neuroscience, Laboratory of Molecular Neurovirology, MERB-757, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, United States.
authors.forename: Jaslyn
authors.initials: J
authors.lastname: Johnson
authors.affiliation: Department of Neuroscience, Laboratory of Molecular Neurovirology, MERB-757, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, United States.
authors.forename: Mohammad
authors.initials: M
authors.lastname: El-Hajmoussa
authors.affiliation: Department of Neuroscience, Laboratory of Molecular Neurovirology, MERB-757, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, United States.
authors.forename: Martyn K
authors.initials: MK
authors.lastname: White
authors.affiliation: Department of Neuroscience, Laboratory of Molecular Neurovirology, MERB-757, Temple University School of Medicine, 3500 N. Broad Street, Philadelphia, PA 19140, United States. Electronic address: msafak@temple.edu.
authors.forename: Mahmut
authors.initials: M
authors.lastname: Safak
mesh_terms: D000595:Amino Acid Sequence; D000957:Antigens, Viral, Tumor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D036022:Capsid Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006801:Humans; D007577:JC Virus / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D008969:Molecular Sequence Data; D027601:Polyomavirus Infections / Q000821:virology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018741:Replication Origin; D014412:Tumor Virus Infections / Q000821:virology*; D014779:Virus Replication
chemical_list: D000957:Antigens, Viral, Tumor; D036022:Capsid Proteins; D004279:DNA, Viral
keywords: BKV; Capsid protein; DNA replication; JCV; Large T antigen; Polyomavirus; Progressive multifocal leukoencephalopathy; SV40; Transcription; VP2; VP3