title: Modulation of PML protein expression regulates JCV infection.
abstract: JC virus (JCV) is a human polyomavirus that infects the majority of the human population worldwide. It is responsible for the fatal demyelinating disease Progressive Multifocal Leukoencephalopathy. JCV binds to cells using the serotonin receptor 5-HT(2A)R and alpha(2-6)- or alpha(2-3)-linked sialic acid. It enters cells using clathrin-dependent endocytosis and traffics to the early endosome and possibly to the endoplasmic reticulum. Viral DNA is then delivered to the nucleus where transcription, replication, and assembly of progeny occur. We found that the early regulatory protein large T antigen accumulates in microdomains in the nucleus adjacent to ND-10 or PML domains. This observation prompted us to explore the role of these domains in JCV infection. We found that a reduction of nuclear PML enhanced virus infection and that an increase in nuclear PML reduced infection. Infection with JCV did not directly modulate nuclear levels of PML but our data indicate that a host response involving interferon beta is likely to restrict virus infection by increasing nuclear PML.
authors.affiliation: Graduate Program in Molecular Biology, Cell Biology and Biochemistry, Brown University, Providence, RI 02912, USA.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Gasparovic
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Maginnis
authors.forename: Bethany A
authors.initials: BA
authors.lastname: O'Hara
authors.forename: Aisling S
authors.initials: AS
authors.lastname: Dugan
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Atwood
mesh_terms: D002460:Cell Line; D002467:Cell Nucleus / Q000821:virology*; D002875:Chromosomes / Q000821:virology*; D006801:Humans; D007577:JC Virus / Q000254:growth & development*; D009687:Nuclear Proteins / Q000378:metabolism*; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070576:PML protein, human