Innate Immune Signalling Induced by Crimean-Congo Haemorrhagic Fever Virus Proteins in Vitro

INNATE IMMUNE SIGNALLING INDUCED BY CRIMEAN-CONGO HAEMORRHAGIC FEVER VIRUS PROTEINS IN VITRO Natalie Viljoen January 2019 INNATE IMMUNE SIGNALLING INDUCED BY CRIMEAN-CONGO HAEMORRHAGIC FEVER VIRUS PROTEINS IN VITRO Natalie Viljoen PhD Medical Virology Submitted in fulfilment of the requirements in respect of the PhD Medical Virology degree completed in the Division of Virology in the Faculty of Health Sciences at the University of the Free State Promoter: Professor Felicity Jane Burt Co-promoter: Professor Dominique Goedhals Division of Virology Faculty of Health Sciences University of the Free State The financial assistance of the National Research Foundation and the Poliomyelitis Research Foundation is hereby acknowledged. Opinions expressed and conclusions arrived at, are those of the author and are not necessarily attributed to these institutions. University of the Free State, Bloemfontein, South Africa January 2019 Table of content Declaration .................................................................................................................. i Acknowledgements ..................................................................................................... ii List of figures .............................................................................................................. iii List of tables ............................................................................................................... iv List of abbreviations ................................................................................................... v Presentations and publications ................................................................................ viii Ethics approval ........................................................................................................... ix Department of Agriculture, Forestry and Fisheries approval ...................................... ix Summary .................................................................................................................... 1 Chapter 1 Introduction, rationale and aims ................................................................ 3 Introduction ............................................................................................................. 3 Problem identification ............................................................................................. 4 Aims and objectives ................................................................................................ 7 Structure of the thesis ............................................................................................. 8 References ............................................................................................................. 9 Chapter 2 Literature review: Crimean-Congo haemorrhagic fever virus.................. 14 Introduction ........................................................................................................... 14 Virus classification and mode of development ...................................................... 15 Epidemiology ........................................................................................................ 18 Genetic variation ................................................................................................... 23 Clinical features .................................................................................................... 24 Diagnosis of infection ............................................................................................ 27 Treatment, prevention and control ........................................................................ 29 Immune response to CCHFV ................................................................................ 32 Pathogenesis ........................................................................................................ 34 CCHF in South Africa ........................................................................................... 37 References ........................................................................................................... 39 Chapter 3 A role for Crimean-Congo haemorrhagic fever virus NSM protein in innate immune modulation .................................................................................................. 56 Authors and author affiliations .............................................................................. 56 Summary .............................................................................................................. 56 Keywords .............................................................................................................. 57 Graphical abstract................................................................................................. 57 Introduction ........................................................................................................... 57 Methods ................................................................................................................ 59 Results .................................................................................................................. 65 Discussion ............................................................................................................ 73 Acknowledgements ............................................................................................... 77 Author contributions .............................................................................................. 77 Declaration of interests ......................................................................................... 77 References ........................................................................................................... 77 Supplemental information ..................................................................................... 84 Chapter 4 Modulation of innate immune signalling by Crimean-Congo haemorrhagic fever virus ovarian tumour-like protease .................................................................. 86 Authors and author affiliations .............................................................................. 86 Summary .............................................................................................................. 86 Keywords .............................................................................................................. 86 Introduction ........................................................................................................... 87 Methods ................................................................................................................ 89 Results .................................................................................................................. 94 Discussion ............................................................................................................ 98 Acknowledgements ............................................................................................. 102 Author contributions ............................................................................................ 102 Declaration of interests ....................................................................................... 102 References ......................................................................................................... 103 Supplemental information ................................................................................... 111 Chapter 5 Characterisation of the innate immune transcriptional response to Hazara virus infection and Hazara viral RNA ...................................................................... 113 Authors and author affiliations ............................................................................ 113 Summary ............................................................................................................ 113 Keywords ............................................................................................................ 113 Introduction ......................................................................................................... 114 Methods .............................................................................................................. 115 Results ................................................................................................................ 121 Discussion .......................................................................................................... 126 Acknowledgements ............................................................................................. 127 Author contributions ............................................................................................ 128 Declaration of interests ....................................................................................... 128 References ......................................................................................................... 128 Supplemental information ................................................................................... 133 Chapter 6 Conclusions and future perspectives .................................................... 134 Appendix A: Letter of ethics approval ..................................................................... 142 Appendix B: Letter of Department of Agriculture, Forestry and Fisheries approval and approval of amendment .......................................................................................... 143 Appendix

Load more