title: Dichloroacetate induces cell cycle arrest in human glioblastoma cells persistently infected with measles virus: a way for controlling viral persistent infection.
abstract: We have previously established a human glioblastoma cell line persistently infected with mutant measles virus (MV), and found increased functions of mitochondria in MV persistently infected cells compared with uninfected or acutely infected cells. Moreover, impairment of mitochondria functions induced a breakdown of persistent infection, which suggested that mitochondria might play an important role in the maintenance of persistent infection and loss or functional alterations of mitochondria might be a candidate for possible intervention in persistent infection. In this study we examined the effect of dichloroacetate (DCA), which is known to increase pyruvate oxidation, on mitochondrial functions in MV persistently infected cells. DCA caused mitochondrial dysfunction and cell cycle arrest in MV persistently infected cells; consequently, the expression level of MV proteins were decreased in a DCA dependent manner. Here, we present a new therapeutic approach for persistent infection targeting mitochondrial respiration. Advantage to targeting mitochondrial respiration is that the impairment of mitochondrial functions by DCA is found in MV persistently infected cells not in uninfected cells, which may offer a promising chemotherapeutic strategy with few adverse effects.
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan. Electronic address: megumi@nms.ac.jp.
authors.forename: Megumi
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Watari
authors.affiliation: Department of Microbiology and Immunology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Hidemi
authors.initials: H
authors.lastname: Takahashi
mesh_terms: D015153:Blotting, Western; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D003999:Dichloroacetic Acid / Q000494:pharmacology*; D005909:Glioblastoma; D006801:Humans; D008459:Measles virus / Q000187:drug effects* / Q000235:genetics; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000032:analysis; D019590:Nucleocapsid Proteins / Q000378:metabolism
chemical_list: D009687:Nuclear Proteins; D019590:Nucleocapsid Proteins; C000590691:measles virus nucleocapsid protein; D003999:Dichloroacetic Acid
keywords: Dichloroacetate; Measles virus; Mitochondria; Persistent infection