The genomics of viral respiratory disease in Australia: Understanding the spread evolution and pathogenesis of non-influenza respiratory viruses
Access status:
Open Access
Type
ThesisThesis type
Doctor of PhilosophyAuthor/s
Tulloch, RachelAbstract
Respiratory disease caused by emerging and endemic viruses present a major threat to public health both locally and globally. Human metapneumovirus (HMPV) is a significant cause of respiratory illness in children and adults, however, little is known about the sources and patterns ...
See moreRespiratory disease caused by emerging and endemic viruses present a major threat to public health both locally and globally. Human metapneumovirus (HMPV) is a significant cause of respiratory illness in children and adults, however, little is known about the sources and patterns of HMPV genetic diversity within Australia, which is important for their control. To address this, I developed an amplicon-based, whole genome sequencing method for HMPV. This assay was then applied to a collection of clinical samples spanning 10 years, that gave the first historical perspective of HMPV genomic diversity in Australia, and assessed the impact of the COVID-19 pandemic, highlighting a major collapse in circulating diversity. Next, I explored the role of metagenomic sequencing (mNGS) in clinical diagnostics of respiratory infections. A proof-of-concept study was performed to evaluate the utility of mNGS in identifying unknown pathogens in a cohort of children with undiagnosed severe acute respiratory illnesses. Several challenges were revealed regarding the use of residual clinical specimens, however, novel finding including the identification of a severe Influenza C virus infection. To facilitate the identification and characterisation of novel and emerging respiratory viruses, a simple and fast mNGS was developed with an aim to provide tangible results in less than 24 hours from sample collection. The RAPIDprep assay was then applied across range of respiratory samples and sources, highlighting the effectiveness of the approach. Ultimately, this research has helped to further our understanding of the epidemiology, transmission and spread of HMPV in Australia, and contributed to the identification of unknown or novel respiratory pathogens using mNGS.
See less
See moreRespiratory disease caused by emerging and endemic viruses present a major threat to public health both locally and globally. Human metapneumovirus (HMPV) is a significant cause of respiratory illness in children and adults, however, little is known about the sources and patterns of HMPV genetic diversity within Australia, which is important for their control. To address this, I developed an amplicon-based, whole genome sequencing method for HMPV. This assay was then applied to a collection of clinical samples spanning 10 years, that gave the first historical perspective of HMPV genomic diversity in Australia, and assessed the impact of the COVID-19 pandemic, highlighting a major collapse in circulating diversity. Next, I explored the role of metagenomic sequencing (mNGS) in clinical diagnostics of respiratory infections. A proof-of-concept study was performed to evaluate the utility of mNGS in identifying unknown pathogens in a cohort of children with undiagnosed severe acute respiratory illnesses. Several challenges were revealed regarding the use of residual clinical specimens, however, novel finding including the identification of a severe Influenza C virus infection. To facilitate the identification and characterisation of novel and emerging respiratory viruses, a simple and fast mNGS was developed with an aim to provide tangible results in less than 24 hours from sample collection. The RAPIDprep assay was then applied across range of respiratory samples and sources, highlighting the effectiveness of the approach. Ultimately, this research has helped to further our understanding of the epidemiology, transmission and spread of HMPV in Australia, and contributed to the identification of unknown or novel respiratory pathogens using mNGS.
See less
Date
2023Rights statement
The author retains copyright of this thesis. It may only be used for the purposes of research and study. It must not be used for any other purposes and may not be transmitted or shared with others without prior permission.Faculty/School
Faculty of Medicine and HealthDepartment, Discipline or Centre
The Westmead Institute for Medical ResearchAwarding institution
The University of SydneyShare