Dichloroacetate induces cell cycle arrest in human glioblastoma cells persistently infected with measles virus: A way for controlling viral persistent infection

• We present a new therapeutic approach for measles virus (MV) persistent infection.
• Dichloroacetate (DCA) caused mitochondrial dysfunction and cell cycle arrest in MV persistently infected cells.
• Expression level of MV proteins were decreased in a DCA dependent manner.

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.