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Characterization of Porcine Enterocytes and Their Susceptibility to Rotavirus

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Characterization of Porcine Enterocytes and Their Susceptibility to Rotavirus Characterization of porcine enterocytes and their susceptibility to rotavirus Word count: 8979 Yana Rommens Student number: 01710629 Supervisor: Prof. Dr. Hans Nauwynck Supervisor: Dr. Sebastiaan Theuns Supervisor: PhD candidate: Nick Vereecke A dissertation submitted to Ghent University in partial fulfilment of the requirements for the degree of Master of Veterinary Medicine Academic year: 2019 - 2020 Ghent University, its employees and/or students, give no warranty that the information provided in this thesis is accurate or exhaustive, nor that the content of this thesis will not constitute or result in any infringement of third-party rights. Ghent University, its employees and/or students do not accept any liability or responsibility for any use which may be made of the content or information given in the thesis, nor for any reliance which may be placed on any advice or information provided in this thesis. Preamble Part of this thesis was supposed to be based on research under the supervision of the Department of Virology. In April 2020, three weeks of experiments were planned to try to shed light on the complicated pathways and morphology of enterocytes in the small intestines of neonatal and older piglets. Finding differences in morphology, expression of receptors and several other factors could be a useful in finding exactly what makes young animals more susceptible to rotavirus. Due to the Covid-19 pandemic all research projects were cancelled and this thesis is now a literature study. As not much is known about the exact reasons why young animals are more sensitive to rotavirus, the second part is much shorter than intended as a result of the absence of data from my own research project. Preface I would like to thank Prof. Dr. Hans Nauwynck for giving me the chance to get to know the lab of virology in the first semester. I would also like to express my thanks to Dr. Sebastiaan Theuns and PhD- candidate Nick Vereecke for their guidance and explanation of the different techniques used in the lab and allowing me to learn them. Their never seizing enthusiasm for their work motivated me and I learned so much. I would also like to thank them for finding the time to correct my thesis and helping me along with their suggestions. In addition to this, I am also grateful for the help of technical assistent Marthe Pauwels who found the time to help me with the different techniques. Finally, I would also like to thank my friends for always offering support. Not only in these last months, but throughout the whole process. Table of contents 1. Summary ............................................................................................................................................... 6 1.1 English summary ............................................................................................................................... 6 1.2 Dutch summary ................................................................................................................................. 6 2. Introduction .......................................................................................................................................... 7 3. Rotavirus ............................................................................................................................................... 8 3.1 Structure of the virus ......................................................................................................................... 8 3.1.1 Genome ..................................................................................................................................... 8 3.1.2 Viral particle ............................................................................................................................... 8 3.2 Classification..................................................................................................................................... 9 3.3 Epidemiology .................................................................................................................................. 10 3.3.1 Zoonotic potential .................................................................................................................... 11 3.4 Replication cycle ............................................................................................................................. 11 3.5 Pathogenesis .................................................................................................................................. 13 3.6 Pathology and clinical signs.............................................................................................................. 13 3.6.1 Macroscopic lesions .................................................................................................................. 13 3.6.2 Histology .................................................................................................................................. 14 3.7 Immunology ................................................................................................................................... 14 3.7.1 Innate immune response ........................................................................................................... 14 3.7.2 Acquired immune response ....................................................................................................... 15 3.7.3 Passive immune response ......................................................................................................... 15 3.8 Prevention ...................................................................................................................................... 15 3.8.1 Hygiene measures .................................................................................................................... 16 3.9 Vaccination ..................................................................................................................................... 16 4. Characteristics of the small intestine ..................................................................................................... 18 4.1 General anatomy of the digestive tract ............................................................................................. 18 4.2 Structure of the small intestine ......................................................................................................... 18 4.2.1 Cells of the epithelium .............................................................................................................. 18 4.2.2 Cell-cell adhesions .................................................................................................................... 19 4.2.3 Cell-matrix adhesions ................................................................................................................ 20 4.3 Changes in small intestine due to aging ............................................................................................ 21 4.3.1 Postpartum .............................................................................................................................. 21 4.3.2 Weaning .................................................................................................................................. 21 4.4 Age-dependent susceptibility............................................................................................................ 22 4.4.1 Influence of TLR3 ...................................................................................................................... 22 4.4.2 Inflammasome ......................................................................................................................... 22 4.4.2 Maturing of gastro-intestinal tract and cells ................................................................................ 23 5. Discussion ........................................................................................................................................... 24 6. References ........................................................................................................................................... 25 1. Summary 1.1 English summary One of the most important problems in piglets is diarrhea. In the gestation unit and shortly after weaning piglets are utmost susceptible to it. Diarrhea can have multiple causes such as viruses, bacteria and parasites. Porcine rotaviruses (RVs) are often a cause of acute viral gastro-enteritis (Theuns, 2015). According to a study conducted by Debouck and Pensaert (1983) the virus is present in almost every farm and will infect almost every pig in the course of their life. The target cells for rotaviruses are the enterocytes of the small intestines. The epithelium of the small intestine consists of different cell types, each with their own function. In addition to this, cell-cell adhesions form a barrier against pathogens including rotaviruses since receptors are found on the basolateral sides of enterocytes and with intact cell-cell adhesions these receptors are less easy to reach. Other factors such as Toll-like receptor 3 seem to play an important role insusceptibility of enterocytes to rotavirus. The intestines are a complex and intriguing part of the gastro-intestinal system and further extensive research is necessary to discover and comprehend all possible receptors, pathways and other factors and mechanisms. Understanding all this could lead to a better healthcare and therefore better production results in intensive farming. 1.2 Dutch summary
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