Thesis
RESPIRATORY SYNCYTIAL VIRUS INFECTION INDUCES NECROPTOTIC LYTIC CELL DEATH VIA ACTIVATION OF ENDOPLASMIC RETICULUM STRESS PATHWAYS
Washington State University
Master of Science (MS), Washington State University
01/2022
DOI:
https://doi.org/10.7273/000004572
Handle:
https://hdl.handle.net/2376/125040
Abstract
Human respiratory syncytial virus (RSV) is a major cause of viral bronchiolitis and pneumonia worldwide. Pneumonia and bronchiolitis during RSV infection are caused by hyper-inflammation in the airway. One of the key factors involved in exaggerated lung inflammation during RSV infection is necroptotic lytic cell death of RSV infected immune cells like macrophages. Intracellular components released in the extracellular milieu due to lytic cell death acts as Damage associated molecular patterns (DAMPs) to exaggerate inflammation. During infection, RSV glycoproteins compete with host proteins to activate ER stress pathway as part of the Unfolded protein response (UPR). ER stress pathway is activated via three ER stress sensors, namely PERK, IRE1 and ATF6. Although RSV infection induce both necroptotic lytic cell death in macrophages, whether RSV utilizes ER stress pathways to induce lytic cell death is unknown. Our study revealed that RSV induces lytic cell death in macrophages by using ATF6 mediated ER stress pathway. RSV infection led to significant induction in ATF6 protein expression. Furthermore, RSV infection resulted in ATF6 activation in macrophages as evident from the detection of the transcriptionally active cleaved ATF6p50 form of ATF6 in RSV infected macrophages. Thus, our studies have demonstrated a positive role of ATF6 dependent ER stress pathway during RSV-mediated necroptotic lytic cell death of macrophages via ATF6 protein induction and activation in RSV infected macrophages.
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Details
- Title
- RESPIRATORY SYNCYTIAL VIRUS INFECTION INDUCES NECROPTOTIC LYTIC CELL DEATH VIA ACTIVATION OF ENDOPLASMIC RETICULUM STRESS PATHWAYS
- Creators
- VIDUSHA KUMUDUHASINI KOTHWELA
- Contributors
- Santanu Bose (Advisor)Massaro W Ueti (Committee Member)Devendra Shah (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Veterinary Medicine, College of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University
- Number of pages
- 48
- Identifiers
- OCLC#: 1370910588; 99900898640901842
- Language
- English
- Resource Type
- Thesis