Epstein-Barr virus as a piece of the neurodegenerative disease mosaic
- UNCG Author/Contributor (non-UNCG co-authors, if there are any, appear on document)
- Ana Paula Carvalho Tognasoli (Creator)
- Institution
- The University of North Carolina at Greensboro (UNCG )
- Web Site: http://library.uncg.edu/
- Advisor
- Amy Adamson
Abstract: Neurodegenerative diseases (ND’s) affect approximately 6 million people in the US, and their incidence and severity is linked to genetic and environmental factors. Human herpesviruses such as Epstein-Barr virus (EBV), were recently implicated as potential infectious agents in the etiology of ND’s. Over 90% of the world’s population has EBV, which initially infects epithelial cells in the nasopharynx to then enter latency in B cells. EBV is a neurotropic virus and can infect astrocytes, neurons, and microglia. In addition, infected B and T cells travel through CNS access areas such as the Glymphatic System and the nasopharynx, where EBV could affect neuronal cell function. Processes such as autophagy, inflammation, and Reactive Oxygen Species (ROS) homeostasis are crucial to ND’s and have already been shown to be affected by EBV. While severe neuronal consequences are rare during EBV infection, little is known about its ability to promote neuronal dysfunction that could prime neuronal cells for ND development. We hypothesized that EBV had the potential to affect neuronal cellular processes that are relevant for the development and establishment of ND’s. To study these interactions in a practical, more easily accessible cell model than primary neuronal cells, we used retinoic-acid (RA) differentiated SH-SY5Y neuroblastoma cells, which have been widely accepted as a suitable cell line for ND studies. We exposed these cells to EBV virions and demonstrated the presence of intracellular viral genome via qPCR. Thus, we are the first ones to show that RA-differentiated SH-SY5Y neuroblastoma cells are permissive to EBV infection. Interestingly, while we did not detect lytic or latent viral transcripts in these cells, our data suggests that EBV-infected neuroblastoma cells have altered ROS homeostasis and decreased mitochondrial function, increased expression of inflammatory markers and autophagic flux block. Overall, we have established that EBV infection of neuronal cells has the potential to affect the neurodegenerative trifecta: ROS, autophagy, and inflammation. Future studies should focus on a more in-depth exploration of each of these processes under EBV infection to elucidate if the virus can act as a piece of the neurodegenerative mosaic.
Epstein-Barr virus as a piece of the neurodegenerative disease mosaic
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Created on 5/1/2022
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Additional Information
- Publication
- Dissertation
- Language: English
- Date: 2022
- Keywords
- Alzheimer's, Epstein-Barr virus, Multiple Sclerosis, Parkinson's, Sh-sy5y
- Subjects
- Nervous system $x Degeneration
- Epstein-Barr virus diseases
- Epstein-Barr virus
- Neuroblastoma