title: Polyomavirus JC infection inhibits differentiation of oligodendrocyte progenitor cells.
abstract: Reactivation of the human polyomavirus JC (JCV) in the CNS results in a fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). The lytic destruction of oligodendrocytes, which occurs at the terminal stage of the viral infection cycle, is considered a critical factor in the development of demyelination and the pathogenesis of PML. However, knowledge is limited about interaction of JCV with oligodendrocytes and its impact on the denudation of axons at the early stage of viral reactivation and prior to the destruction of the infected cells. We have developed an in vitro neuroprogenitor cell culture using human fetal brain that can be differentiated to the oligodendrocyte lineage to investigate interactions of JCV with its host cells. Results show that infection with JCV delays oligodendrocyte maturation as shown by reduced levels of oligodendrocytic markers, including myelin basic protein, proteolipid protein, and platelet-derived growth factor receptor-α. Furthermore, replication of JCV in these cells caused substantial dysregulation of several chemokines, including CCL5/RANTES, GRO, CXCL1/GROα, CXCL16, CXCL8/IL-8, CXCL5/ENA-78, and CXCL10/IP-10, all of which play a role in cell growth and differentiation.
authors.affiliation: Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Armine
authors.initials: A
authors.lastname: Darbinyan
authors.forename: Rafal
authors.initials: R
authors.lastname: Kaminski
authors.forename: Martyn K
authors.initials: MK
authors.lastname: White
authors.forename: Nune
authors.initials: N
authors.lastname: Darbinian-Sarkissian
authors.forename: Kamel
authors.initials: K
authors.lastname: Khalili
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007968:Leukoencephalopathy, Progressive Multifocal / Q000378:metabolism / Q000821:virology; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism / Q000821:virology*; D027601:Polyomavirus Infections / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014412:Tumor Virus Infections / Q000378:metabolism
chemical_list: D018925:Chemokines