Altered Mitochondrial Dynamics in Venezuelan Equine Encephalitis Virus Infected Cells
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Brooks-Faulconer, Taryn
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Abstract
To establish productive infection, viruses profoundly alter both the intracellular environment and the cellular function. Mitochondria are critically important cellular organelles that generate energy and ensure cell survival. Mitochondria are also crucial for innate immunity response as they serve as the sentinels that sense infection and initiate host responses. For many viruses, the changes in mitochondrial dynamics were documented to occur early in infection. Venezuelan Equine Encephalitis Virus (VEEV) is a New World alphavirus that infects neuronal cells and produces an encephalitic phenotype. In this manuscript, we demonstrate that VEEV infection results in mitochondrial alterations that include changes in the morphology and intracellular distribution of mitochondria, reduction in mitochondrial membrane potential and localization of their enzymatic components. In particular, we report perinuclear accumulation of mitochondria in infected cells and partial co-localization of the viral capsid proteins with mitochondrial membranes. The pronounced changes to the mitochondria observed in VEEV infected cells probably play a role in the development of the virus-specific cytopathic effects. Our studies demonstrate that the mitochondria are critical intracellular platforms affected by alphavirus infections.
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This thesis has been embargoed for 1 year and will not be available until April 2017.
Keywords
New World alphavirus, Reactive oxygen species, Membrane potential, Venezuelan Equine Encephalitis virus, Mitochondria, Perinuclear clustering