title: Measles Virus Infection Inactivates Cellular Protein Phosphatase 5 with Consequent Suppression of Sp1 and c-Myc Activities.
abstract: Measles virus (MeV) causes several unique syndromes, including transient immunosuppression. To clarify the cellular responses to MeV infection, we previously analyzed a MeV-infected epithelial cell line and a lymphoid cell line by microarray and showed that the expression of numerous genes was up- or downregulated in the epithelial cells. In particular, there was a characteristic comprehensive downregulation of housekeeping genes during late stage infection. To identify the mechanism underlying this phenomenon, we examined the phosphorylation status of transcription factors and kinase/phosphatase activities in epithelial cells after infection. MeV infection inactivated cellular protein phosphatase 5 (PP5) that consequently inactivated DNA-dependent protein kinase, which reduced Sp1 phosphorylation levels, and c-Myc degradation, both of which downregulated the expression of many housekeeping genes. In addition, intracellular accumulation of viral nucleocapsid inactivated PP5 and subsequent downstream responses. These findings demonstrate a novel strategy of MeV during infection, which causes the collapse of host cellular functions.
  
  
  OBJECTIVE
  Measles virus (MeV) is one of the most important pathogens in humans. We previously showed that MeV infection induces the comprehensive downregulation of housekeeping genes in epithelial cells. By examining this phenomenon, we clarified the molecular mechanism underlying the constitutive expression of housekeeping genes in cells, which is maintained by cellular protein phosphatase 5 (PP5) and DNA-dependent protein kinase. We also demonstrated that MeV targets PP5 for downregulation in epithelial cells. This is the first report to show how MeV infection triggers a reduction in overall cellular functions of infected host cells. Our findings will help uncover unique pathogenicities caused by MeV.
authors.affiliation: Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sato
authors.affiliation: Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Misako
authors.initials: M
authors.lastname: Yoneda
authors.affiliation: Clinical Informatics, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Honma
authors.affiliation: Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Fusako
authors.initials: F
authors.lastname: Ikeda
authors.affiliation: Clinical Informatics, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan ckai@ims.u-tokyo.ac.jp.
authors.forename: Chieko
authors.initials: C
authors.lastname: Kai
mesh_terms: D017931:DNA Primers / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D004847:Epithelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D008156:Luciferases; D008457:Measles / Q000503:physiopathology*; D008459:Measles virus; D046228:Microarray Analysis; D009687:Nuclear Proteins / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids / Q000235:genetics; D011494:Protein Kinases / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism
chemical_list: D017931:DNA Primers; C489427:MYC protein, human; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D008156:Luciferases; D011494:Protein Kinases; C065999:Sp1 kinase; D010749:Phosphoprotein Phosphatases; C089641:protein phosphatase 5