Characterisation of emergent and emerging human-infective RNA viruses
<p>Improved understanding of the early adaptation of zoonotic, human-infective RNA viruses and the genetic factors leading to spillover will inform public health approaches attempting to limit the morbidity and mortality associated with these events. In this thesis, I use clinical microbiologi...
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| Other Authors: | |
| Format: | Thesis |
| Language: | English |
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2022
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| _version_ | 1826315650114519040 |
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| author | Ratcliff, J |
| author2 | Simmonds, P |
| author_facet | Simmonds, P Ratcliff, J |
| author_sort | Ratcliff, J |
| collection | OXFORD |
| description | <p>Improved understanding of the early adaptation of zoonotic, human-infective RNA viruses and the genetic factors leading to spillover will inform public health approaches attempting to limit the morbidity and mortality associated with these events. In this thesis, I use clinical microbiological methods to characterize the intra-host replicative and evolutionary dynamics of SARS-CoV-2 and bioinformatic approaches to investigate genetic factors associated with spillover of arboviruses.</p>
<p>Chapter one broadly reviews the field of virology.</p>
<p>Chapter two reviews the apolipoprotein B mRNA-editing enzyme, catalytic polypeptide (APOBEC) family of proteins, focusing on their emergence, diversification, and function, and summarizes the bioinformatic and functional evidence of their role in SARS-CoV-2 evolution.</p>
<p>Chapter three details the methods underlying the subsequent results chapters.</p>
<p>Chapter four describes the development and validation of single nucleotide polymorphism-based genotyping assays for identifying variants of concern in COVID-19 clinical samples. Their performance is compared to next-generation sequencing, demonstrating the superiority of the genotyping assays at a wide range of viral loads.</p>
<p>Chapter five uses amplification data generated from two COVID-19 clinical trials to explore factors associated with viral load and within-patient viral load dynamics, uses a novel polymerase chain reaction approach to quantify subgenomic RNA transcripts, and investigates the emergence and spread of the Alpha variant in the United Kingdom and the Zeta, Gamma, and Delta variants in Brazil.</p>
<p>Chapter six investigates the interaction between SARS-CoV-2 virological features and COVID-19 clinical outcomes leveraging patients admitted to intensive care within the REMAP-CAP convalescent plasma clinical trial. The null results in this chapter support severe COVID-19 pathology being primarily immune-mediated.</p>
<p>Chapter seven quantitatively tests the hypothesis that convalescent plasma treatment was responsible for the emergence of SARS-CoV-2 variants of concern using an intensively sampled cohort within the REMAP-CAP convalescent plasma trial. Using a variety of approaches, no evidence in support of convalescent plasma therapy as a general driver of immune-escape substitutions was found.</p>
<p>Chapter eight probes the genetic factors associated with human-human transmissibility of arboviruses, finding strong evidence for the role of CpG suppression in the host optimization of flaviviruses. The strong genetic barriers to spillover enable more focused surveillance of this informal classification of viruses.</p> |
| first_indexed | 2024-03-07T07:41:55Z |
| format | Thesis |
| id | oxford-uuid:103dfddd-519b-410c-a253-80490e4fe26b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-12-09T03:29:59Z |
| publishDate | 2022 |
| record_format | dspace |
| spelling | oxford-uuid:103dfddd-519b-410c-a253-80490e4fe26b2024-12-01T13:19:50ZCharacterisation of emergent and emerging human-infective RNA virusesThesishttp://purl.org/coar/resource_type/c_db06uuid:103dfddd-519b-410c-a253-80490e4fe26bVirologyEnglishHyrax Deposit2022Ratcliff, JSimmonds, PSmith, AHarvala, H<p>Improved understanding of the early adaptation of zoonotic, human-infective RNA viruses and the genetic factors leading to spillover will inform public health approaches attempting to limit the morbidity and mortality associated with these events. In this thesis, I use clinical microbiological methods to characterize the intra-host replicative and evolutionary dynamics of SARS-CoV-2 and bioinformatic approaches to investigate genetic factors associated with spillover of arboviruses.</p> <p>Chapter one broadly reviews the field of virology.</p> <p>Chapter two reviews the apolipoprotein B mRNA-editing enzyme, catalytic polypeptide (APOBEC) family of proteins, focusing on their emergence, diversification, and function, and summarizes the bioinformatic and functional evidence of their role in SARS-CoV-2 evolution.</p> <p>Chapter three details the methods underlying the subsequent results chapters.</p> <p>Chapter four describes the development and validation of single nucleotide polymorphism-based genotyping assays for identifying variants of concern in COVID-19 clinical samples. Their performance is compared to next-generation sequencing, demonstrating the superiority of the genotyping assays at a wide range of viral loads.</p> <p>Chapter five uses amplification data generated from two COVID-19 clinical trials to explore factors associated with viral load and within-patient viral load dynamics, uses a novel polymerase chain reaction approach to quantify subgenomic RNA transcripts, and investigates the emergence and spread of the Alpha variant in the United Kingdom and the Zeta, Gamma, and Delta variants in Brazil.</p> <p>Chapter six investigates the interaction between SARS-CoV-2 virological features and COVID-19 clinical outcomes leveraging patients admitted to intensive care within the REMAP-CAP convalescent plasma clinical trial. The null results in this chapter support severe COVID-19 pathology being primarily immune-mediated.</p> <p>Chapter seven quantitatively tests the hypothesis that convalescent plasma treatment was responsible for the emergence of SARS-CoV-2 variants of concern using an intensively sampled cohort within the REMAP-CAP convalescent plasma trial. Using a variety of approaches, no evidence in support of convalescent plasma therapy as a general driver of immune-escape substitutions was found.</p> <p>Chapter eight probes the genetic factors associated with human-human transmissibility of arboviruses, finding strong evidence for the role of CpG suppression in the host optimization of flaviviruses. The strong genetic barriers to spillover enable more focused surveillance of this informal classification of viruses.</p> |
| spellingShingle | Virology Ratcliff, J Characterisation of emergent and emerging human-infective RNA viruses |
| title | Characterisation of emergent and emerging human-infective RNA viruses |
| title_full | Characterisation of emergent and emerging human-infective RNA viruses |
| title_fullStr | Characterisation of emergent and emerging human-infective RNA viruses |
| title_full_unstemmed | Characterisation of emergent and emerging human-infective RNA viruses |
| title_short | Characterisation of emergent and emerging human-infective RNA viruses |
| title_sort | characterisation of emergent and emerging human infective rna viruses |
| topic | Virology |
| work_keys_str_mv | AT ratcliffj characterisationofemergentandemerginghumaninfectivernaviruses |