The Effect of Cellular Autophagy on Replication and Dissemination of Theiler's Murine Encephalomyelitis Virus

Abstract

Autophagy is a catabolic pathway that enables the cell to sequester and degrade cytoplasmic contents and also serves as an innate response against intracellular pathogens. Many viruses have evolved to subvert this fundamental pathway for their own replication and spread. For example, poliovirus uses autophagy for replication and nonlytic dissemination. However, the replication and spread of rhinovirus type 2 has been shown to be unaffected by autophagic induction and inhibition. Theiler's Murine Encephalomyelitis Virus (TMEV), a related picornavirus, causes a demyelinating disease that serves as a model for multiple sclerosis. The effect of autophagy on cell viability, viral replication, and viral spread in TMEV infected cells has not been elucidated. By immunofluorescence staining and confocal microscopy, we have demonstrated that the 3D polymerase colocalizes with the autophagosomal marker microtubule‐associated protein light chain 3 (LC3). Furthermore, western blotting shows significant LC3 upregulation during the course of TMEV infection. Therefore, TMEV likely regulates the autophagic pathway for its replication and spread. Further understanding of how the virus utilizes autophagy may lead to novel insights regarding TMEV‐induced demyelinating disease.