title: Peroxiredoxin 1 is required for efficient transcription and replication of measles virus.
abstract: Measles is a highly contagious human disease caused by the measles virus (MeV). In this study, by proteomic analysis, we identified peroxiredoxin 1 (Prdx1) as a host factor that binds to the C-terminal region of the nucleoprotein (N; N(TAIL)) of MeV. Glutathione S-transferase (GST) pulldown experiments showed that the Prdx1-binding site overlapped with the MeV phosphoprotein (P)-binding site on N(TAIL) and that Prdx1 competed for the binding to N(TAIL) with the P protein, which is a component of RNA-dependent RNA polymerase (RdRp). Furthermore, RNA interference for Prdx1 resulted in a significant reduction in MeV growth in HEK293-SLAM cells. A minigenome assay indicated that Prdx1 suppression affected the viral RNA transcription and/or replication step. Relative quantification of viral RNA by real-time PCR (RT-PCR) showed that Prdx1 suppression not only reduced viral RNA transcription and replication but also enhanced polar attenuation in viral mRNA transcription. Surface plasmon resonance analysis showed that the binding affinity of Prdx1 to MeV-N was 40-fold lower than that of MeV-P to MeV-N, which suggested that Prdx1 might be involved in the early stage of MeV infection, when the expression level of Prdx1 was much higher than that of MeV-P. Since Prdx1 was expressed abundantly and constitutively in various cells, the results in this study indicate that Prdx1 is one of the inherent host factors implicated in MeV RNA synthesis.
authors.affiliation: The Institute of Medical Sciences, The University of Tokyo, 4-6-1 Shirokanedai, Tokyo 108-8639, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Watanabe
authors.forename: Misako
authors.initials: M
authors.lastname: Yoneda
authors.forename: Fusako
authors.initials: F
authors.lastname: Ikeda
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sugai
authors.forename: Hiroki
authors.initials: H
authors.lastname: Sato
authors.forename: Chieko
authors.initials: C
authors.lastname: Kai
mesh_terms: D001665:Binding Sites; D015967:Gene Expression Regulation, Viral; D057809:HEK293 Cells; D006801:Humans; D008457:Measles / Q000201:enzymology* / Q000821:virology; D008459:Measles virus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D054464:Peroxiredoxins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D014764:Viral Proteins; C058314:nucleoprotein, Measles virus; D054464:Peroxiredoxins