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Comparative Respiratory Tract Pathology of Emerging Viral Infections Laura Baseler Purdue University

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Comparative Respiratory Tract Pathology of Emerging Viral Infections Laura Baseler Purdue University Purdue University Purdue e-Pubs Open Access Dissertations Theses and Dissertations January 2015 Comparative Respiratory Tract Pathology of Emerging Viral Infections Laura Baseler Purdue University Follow this and additional works at: https://docs.lib.purdue.edu/open_access_dissertations Recommended Citation Baseler, Laura, "Comparative Respiratory Tract Pathology of Emerging Viral Infections" (2015). Open Access Dissertations. 1165. https://docs.lib.purdue.edu/open_access_dissertations/1165 This document has been made available through Purdue e-Pubs, a service of the Purdue University Libraries. Please contact [email protected] for additional information. Graduate School Form 30 Updated 1/15/2015 PURDUE UNIVERSITY GRADUATE SCHOOL Thesis/Dissertation Acceptance This is to certify that the thesis/dissertation prepared By Laura Jean Baseler Entitled COMPARATIVE RESPIRATORY TRACT PATHOLOGY OF EMERGING VIRAL INFECTIONS For the degree of Doctor of Philosophy Is approved by the final examining committee: Margaret Miller R. Mark Simpson Co-chair Heinz Feldmann Co-chair Roman Pogranichniy Ramesh Vemulapalli To the best of my knowledge and as understood by the student in the Thesis/Dissertation Agreement, Publication Delay, and Certification Disclaimer (Graduate School Form 32), this thesis/dissertation adheres to the provisions of Purdue University’s “Policy of Integrity in Research” and the use of copyright material. Approved by Major Professor(s): Margaret Miller & Heinz Feldmann Approved by: Ramesh Vemulapalli 7/7/2015 Head of the Departmental Graduate Program Date i COMPARATIVE RESPIRATORY TRACT PATHOLOGY OF EMERGING VIRAL INFECTIONS A Dissertation Submitted to the Faculty of Purdue University by Laura J. Baseler In Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy August 2015 Purdue University West Lafayette, Indiana ii ACKNOWLEDGEMENTS I would like to thank all members of the Laboratory of Virology at the Rocky Mountain Laboratories and the Rocky Mountain Veterinary Branch, particularly Emmie de Wit and Dana P. Scott for their invaluable contributions. I would also like to acknowledge all of the advice and help offered by my graduate committee members. Finally, I especially want to thank the National Institutes of Health Comparative Biomedical Scientist Training Program for providing me with the amazing opportunity to obtain a Ph.D. iii TABLE OF CONTENTS Page LIST OF TABLES ............................................................................................................. ix LIST OF FIGURES ........................................................................................................... xi ABSTRACT ..................................................................................................................... xiii CHAPTER 1. INTRODUCTION ....................................................................................... 1 1.1 Emerging Infectious Diseases .............................................................................. 1 1.2 Nipah Virus .......................................................................................................... 2 1.2.1 The Initial Outbreak ...................................................................................... 2 1.2.2 The Emergence of Nipah Virus in Bangladesh and India ............................. 4 1.2.3 A Comparison of Nipah Virus Outbreaks ..................................................... 5 1.2.4 Nipah Virus Tissue Tropism and Host Range .............................................. 7 1.2.5 Animal Models of Nipah Virus Infection ..................................................... 8 1.2.5.1 Mouse Models of Nipah Virus Infection.................................................. 8 1.2.5.2 A Domestic Cat Model of Nipah Virus Infection .................................... 9 1.2.5.3 A Chicken Embryo Model of Nipah Virus Infection ............................. 10 1.2.5.4 A Guinea Pig Model of Nipah Virus Infection ...................................... 10 1.2.5.5 A Ferret Model of Nipah Virus Infection............................................... 11 1.2.5.6 An African Green Monkey Model of Nipah Virus Infection .................. 11 iv Page 1.2.5.7 A Syrian Hamster Model of Nipah Virus Infection ............................... 12 1.2.6 A Second RNA Virus Emerges in Humans ................................................ 14 1.3 Middle East Respiratory Syndrome Coronavirus (MERS-CoV) ....................... 14 1.3.1 The Emergence of MERS-CoV .................................................................. 14 1.3.2 Human MERS-CoV Infections ................................................................... 15 1.3.3 MERS-CoV Transmission .......................................................................... 16 1.3.4 The Pathology of MERS-CoV (and SARS-CoV) in Humans .................... 19 1.3.5 Tissue Tropism and Host Range of MERS-CoV ........................................ 20 1.3.6 Animal Models of MERS-CoV Infection ................................................... 21 1.4 Conclusion and Hypotheses ............................................................................... 22 1.5 References .......................................................................................................... 23 CHAPTER 2. SYRIAN HAMSTERS (MESOCRICETUS AURATUS) ORONASALLY INOCULATED WITH A NIPAH VIRUS ISOLATE FROM BANGLADESH OR MALAYSIA DEVELOP SIMILAR RESPIRATORY TRACT LESIONS ..................... 49 2.1 Abstract ............................................................................................................... 50 2.2 Introduction ........................................................................................................ 51 2.3 Materials and Methods ....................................................................................... 53 2.3.1 Ethics Statement.......................................................................................... 53 2.3.2 Case Selection and Histology ..................................................................... 53 2.3.3 Immunohistochemistry ............................................................................... 54 2.3.4 Statistical Analysis ...................................................................................... 55 2.4 Results ................................................................................................................ 55 2.4.1 Nasal Cavity ................................................................................................ 55 v Page 2.4.2 Lung ............................................................................................................ 57 2.4.3 Pulmonary Vasculature ............................................................................... 58 2.4.4 Brain ............................................................................................................ 59 2.5 Discussion ........................................................................................................... 59 2.6 Acknowledgements ............................................................................................ 62 2.7 Funding ............................................................................................................... 62 2.8 References .......................................................................................................... 62 CHAPTER 3. DEFINING EARLY TARGET CELLS OF NIPAH VIRUS INFECTION…………………………………………………………………………….. 74 3.1 Abstract ............................................................................................................... 75 3.2 Introduction ........................................................................................................ 76 3.3 Materials and Methods ....................................................................................... 78 3.3.1 Ethics Statement.......................................................................................... 78 3.3.2 Virus and Cells ............................................................................................ 78 3.3.3 Animal Experiments ................................................................................... 79 3.3.4 Histology, Immunohistochemistry and In Situ Hybridization .................... 79 3.3.5 Quantitative Real-Time RT-PCR (qRT-PCR) ............................................ 80 3.3.6 Virus Titrations ........................................................................................... 81 3.4 Results ................................................................................................................ 81 3.4.1 Nipah Virus Replication is Detected at 8 Hours Post Inoculation .............. 81 3.4.2 Nipah Virus Initially Targets the Lung and Nasal Cavity .......................... 82 3.4.3 Nipah Virus Spreads from Nasal Cavity or Lung to Trachea and Larynx .. 83 3.4.4 Nipah Virus Disseminates Outside of the Respiratory Tract ...................... 84 vi Page 3.4.5 NiV-B Mirrors the Early Target Cells of NiV-M yet Exhibits Slower Virus Dissemination ............................................................................................................ 85 3.5 Discussion ........................................................................................................... 86 3.6 Acknowledgements ............................................................................................ 90 3.7 Funding ..............................................................................................................
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