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Subversion of Host Cell Mitochondria by RSV to Favor Virus Production is Dependent on Inhibition of Mitochondrial Complex I and ROS Generation
Respiratory syncytial virus (RSV) is a key cause of severe respiratory infection in infants, immunosuppressed adults, and the elderly worldwide, but there is no licensed vaccine or effective, widely-available antiviral therapeutic. We recently reported staged redistribution of host cell mitochondria...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912631/ https://www.ncbi.nlm.nih.gov/pubmed/31717900 http://dx.doi.org/10.3390/cells8111417 |
Sumario: | Respiratory syncytial virus (RSV) is a key cause of severe respiratory infection in infants, immunosuppressed adults, and the elderly worldwide, but there is no licensed vaccine or effective, widely-available antiviral therapeutic. We recently reported staged redistribution of host cell mitochondria in RSV infected cells, which results in compromised respiratory activities and increased reactive oxygen species (ROS) generation. Here, bioenergetic measurements, mitochondrial redox-sensitive dye, and high-resolution quantitative imaging were performed, revealing for the first time that mitochondrial complex I is key to this effect on the host cell, whereby mitochondrial complex I subunit knock-out (KO) cells, with markedly decreased mitochondrial respiration, show elevated levels of RSV infectious virus production compared to wild-type cells or KO cells with re-expressed complex I subunits. This effect correlates strongly with elevated ROS generation in the KO cells compared to wild-type cells or retrovirus-rescued KO cells re-expressing complex I subunits. Strikingly, blocking mitochondrial ROS levels using the mitochondrial ROS scavenger, mitoquinone mesylate (MitoQ), inhibits RSV virus production, even in the KO cells. The results highlight RSV’s unique ability to usurp host cell mitochondrial ROS to facilitate viral infection and reinforce the idea of MitoQ as a potential therapeutic for RSV. |
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