Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/134955
Title: DEVELOPMENT OF A MURINE MODEL OF EV71 INFECTION, DISEASE AND PATHOLOGY USING MOUSE CELL ADAPTED STRAINS
Authors: CARLA BIANCA LUENA VICTORIO
Keywords: enterovirus 71, mouse infection model, neurogenic pulmonary edema, EV-A71, histopathology, immunohistochemistry
Issue Date: 27-Jul-2016
Citation: CARLA BIANCA LUENA VICTORIO (2016-07-27). DEVELOPMENT OF A MURINE MODEL OF EV71 INFECTION, DISEASE AND PATHOLOGY USING MOUSE CELL ADAPTED STRAINS. ScholarBank@NUS Repository.
Abstract: Enterovirus 71 (EV-A71) is now the most common neurotropic enterovirus. It causes Hand, Foot, and Mouth Disease (HFMD) and occasional outbreaks of severe neurological deficits in infected children. Current animal infection models using NHPs and rodents recapitulate some features of the wide clinical spectrum of illnesses induced by EV-A71 infection in humans. However, none of these recapitulates the key clinical and pathological features of EV-A71-induced neurogenic pulmonary edema (NPE) observed in majority of fatal human cases. We developed an infection model by inoculating one-week-old BALB/c mice with novel viral strains that productively infect rodent and primate cell lines. These mouse-cell-adapted (MCA-EV-A71) strains were generated by serial passage of a brainstem clinical isolate (EV71:BS) in a murine embryonic fibroblast (NIH/3T3) cell line. These strains infected rodent cell lines using the physiologically expressed EV-A71 receptor, SCARB2 (Scavenger Receptor Class B, Member-2). In addition, three amino acid substitutions in VP1 (K98E, E145A, and L169F) are necessary and sufficient to enable the virus to productively infect rodent cells. Mice inoculated with MCA-EV-A71 strains exhibited acute, severe disease, and some exhibited respiratory distress. Gross pathological features are consistent with pulmonary edema, and further histopathological analyses and biochemical tests confirmed the onset of NPE in this subset of mice with overt respiratory distress. This mouse model represents the first valid animal model of EV-A71 infection that also exhibits NPE. We hope to use this system to further understand the neuropathogenesis of EV-A71, especially in the context of NPE induction.
URI: http://scholarbank.nus.edu.sg/handle/10635/134955
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002_CHAPTER 1 - LITERATURE REVIEW.pdf1.3 MBAdobe PDF

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003_CHAPTER 2 - MATERIALS AND METHODS.pdf1.7 MBAdobe PDF

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004_CHAPTER 3 - PHENOTYPIC AND GENOTYPIC CHARACTERISTICS.pdf2.66 MBAdobe PDF

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005_CHAPTER 4 - GENETIC FEATURES OF MCA-EV-A71 STRAINS.pdf2.84 MBAdobe PDF

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006_CHAPTER 5 - CLINICAL DISEASE INDUCED BY MCA-EV-A71 STRAINS.pdf1.79 MBAdobe PDF

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007_CHAPTER 6 - GENERAL PATHOLOGY INDUCED BY MCA-EV-A71.pdf4.55 MBAdobe PDF

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008_CHAPTER 7 - NEUROPATHOLOGY INDUCED BY MCA-EV-A71.pdf3.22 MBAdobe PDF

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009_CHAPTER 8 - CONCLUSION AND PERSPECTIVES.pdf797.76 kBAdobe PDF

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010_CHAPTER 9 - BIBLIOGRAPHY.pdf740.14 kBAdobe PDF

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001_FRONT PAGE.pdf1.05 MBAdobe PDF

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011_APPENDIX A.pdf6.45 MBAdobe PDF

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012_APPENDIX B.pdf5.62 MBAdobe PDF

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013_APPENDIX C.pdf13.65 MBAdobe PDF

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