التفاصيل البيبلوغرافية
| العنوان: |
Investigating the role of viroplasm formation and calcium levels on the production of prostaglandin E₂ during rotavirus infection |
| المؤلفون: |
Sander, Willem Jacobus |
| المساهمون: |
O'Neill, H. G., Pohl-Albertyn, C. H. |
| بيانات النشر: |
University of the Free State |
| سنة النشر: |
2022 |
| مصطلحات موضوعية: |
Rotavirus, internalisation, viroplasms, prostaglandin E2, cytoplasmic calcium, cytoplasmic phospholipase A2, NSP4, NSP5 |
| الوصف: |
Thesis (Ph.D.(Microbiology))--University of the Free State, 2022 ; Both in vitro and in vivo studies have shown that levels of prostaglandin E₂ (PGE₂), an immunomodulatory eicosanoid, are increased during rotavirus (RV) infection. Although it has been shown that inhibition of cyclooxygenase (COX) (PGE₂ biomes) has adverse effects on viral yield, the mechanism of PGE₂ induction during replication remains unknown. Viroplasms are viral factories that consist of several viral proteins, in particular NSP2 and NSP5, and cellular lipid droplets. Lipid droplets (LDs), with their high content of neutral lipids and the proximity of PGE₂ biosynthetic enzymes, are well known sites for PGE₂ biosynthesis. In addition, during replication, RV has been shown to increase the total lipid content of infected cells, while modulating specific lipid classes during infection. Inhibitors that prevent the formations of LDs severely limit the amount of viroplasms formed and subsequently decrease viral progeny production. Another viral protein critical for viral replication is the enterotoxin, NSP4. NSP4, contains a viroporin domain that selectively conducts calcium (Ca²⁺) from the endoplasmic reticulum to the cytosol, increasing free intracellular Ca²⁺. Intracellular Ca²⁺ levels are crucial for the activation and function of cytoplasmic phospholipase A₂, the rate-limiting enzyme in PGE₂ biosynthesis. Both LDs and phospholipase A₂ are also essential for PGE₂ biosynthesis. Therefore, the main objective of the study was to determine when and by which mechanism(s) RV induces/amplifies the production of prostaglandin E₂. During early infection, RV attaches to several cellular receptors and enters the cells by either clathrin-dependent or -independent endocytosis. Other viruses such as bovine ephemeral fever virus haven been shown to require the activation COX-2-mediated PGE₂/EP receptor signalling for enhanced clathrin-mediated endocytosis. To determine if PGE₂ exerts its proviral effects during internalisation we supplemented MA104 cells with ... |
| نوع الوثيقة: |
thesis |
| وصف الملف: |
application/pdf |
| اللغة: |
English |
| العلاقة: |
http://hdl.handle.net/11660/12315Test |
| الإتاحة: |
http://hdl.handle.net/11660/12315Test |
| حقوق: |
University of the Free State |
| رقم الانضمام: |
edsbas.ACB16C0 |
| قاعدة البيانات: |
BASE |
