Exploring the phylodynamics, genetic reassortment and RNA secondary structure formation patterns of orthomyxoviruses by comparative sequence analysis

dc.contributor.advisorMartin, Darren
dc.contributor.authorNindo, Fredrick Nzabanyi
dc.date.accessioned2020-04-30T08:18:21Z
dc.date.available2020-04-30T08:18:21Z
dc.date.issued2019
dc.date.updated2020-04-30T07:18:07Z
dc.description.abstractRNA viruses are among the most virulent microorganisms that threaten the health of humans and livestock. Among the most socio-economically important of the known RNA viruses are those found in the family Orthomyxovirus. In this era of rapid low-cost genome sequencing and advancements in computational biology techniques, many previously difficult research questions relating to the molecular epidemiology and evolutionary dynamics of these viruses can now be answered with ease. Using sequence data together with associated meta-data, in chapter two of this dissertation I tested the hypothesis that the Influenza A/H1N1 2009 pandemic virus was introduced multiple times into Africa, and subsequently dispersed heterogeneously across the continent. I further tested to what degree factors such as road distances and air travel distances impacted the observed pattern of spread of this virus in Africa using a generalised linear modelbased approach. The results suggested that their were multiple simultaneous introductions of 2009 pandemic A/H1N1 into Africa, and geographical distance and human mobility through air travel played an important role towards dissemination. In chapter three, I set out to test two hypotheses: (1) that there is no difference in the frequency of reassortments among the segments that constitute influenza virus genomes; and (2) that there is epochal temporal reassortment among influenza viruses and that all geographical regions are equally likely sources of epidemiologically important influenza virus reassortant lineages. The findings suggested that surface segments are more frequently exchanges than internal genes and that North America/Asia, Oceania, and Asia could be the most likely source locations for reassortant Influenza A, B and C virus lineages respectively. In chapter four of this thesis, I explored the formation of RNA secondary structures within the genomes of orthomyxoviruses belonging to five genera: Influenza A, B and C, Infectious Salmon Anaemia Virus and Thogotovirus using in silico RNA folding predictions and additional molecular evolution and phylogenetic tests to show that structured regions may be biologically functional. The presence of some conserved structures across the five genera is likely a reflection of the biological importance of these structures, warranting further investigation regarding their role in the evolution and possible development of antiviral resistance. The studies herein demonstrate that pathogen genomics-based analytical approaches are useful both for understanding the mechanisms that drive the evolution and spread of rapidly evolving viral pathogens such as orthomyxoviruses, and for illuminating how these approaches could be leveraged to improve the management of these pathogens.
dc.identifier.apacitationNindo, F. N. (2019). <i>Exploring the phylodynamics, genetic reassortment and RNA secondary structure formation patterns of orthomyxoviruses by comparative sequence analysis</i>. (). ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences. Retrieved from en_ZA
dc.identifier.chicagocitationNindo, Fredrick Nzabanyi. <i>"Exploring the phylodynamics, genetic reassortment and RNA secondary structure formation patterns of orthomyxoviruses by comparative sequence analysis."</i> ., ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2019. en_ZA
dc.identifier.citationNindo, F.N. 2019. Exploring the phylodynamics, genetic reassortment and RNA secondary structure formation patterns of orthomyxoviruses by comparative sequence analysis. . ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences. en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Nindo, Fredrick Nzabanyi AB - RNA viruses are among the most virulent microorganisms that threaten the health of humans and livestock. Among the most socio-economically important of the known RNA viruses are those found in the family Orthomyxovirus. In this era of rapid low-cost genome sequencing and advancements in computational biology techniques, many previously difficult research questions relating to the molecular epidemiology and evolutionary dynamics of these viruses can now be answered with ease. Using sequence data together with associated meta-data, in chapter two of this dissertation I tested the hypothesis that the Influenza A/H1N1 2009 pandemic virus was introduced multiple times into Africa, and subsequently dispersed heterogeneously across the continent. I further tested to what degree factors such as road distances and air travel distances impacted the observed pattern of spread of this virus in Africa using a generalised linear modelbased approach. The results suggested that their were multiple simultaneous introductions of 2009 pandemic A/H1N1 into Africa, and geographical distance and human mobility through air travel played an important role towards dissemination. In chapter three, I set out to test two hypotheses: (1) that there is no difference in the frequency of reassortments among the segments that constitute influenza virus genomes; and (2) that there is epochal temporal reassortment among influenza viruses and that all geographical regions are equally likely sources of epidemiologically important influenza virus reassortant lineages. The findings suggested that surface segments are more frequently exchanges than internal genes and that North America/Asia, Oceania, and Asia could be the most likely source locations for reassortant Influenza A, B and C virus lineages respectively. In chapter four of this thesis, I explored the formation of RNA secondary structures within the genomes of orthomyxoviruses belonging to five genera: Influenza A, B and C, Infectious Salmon Anaemia Virus and Thogotovirus using in silico RNA folding predictions and additional molecular evolution and phylogenetic tests to show that structured regions may be biologically functional. The presence of some conserved structures across the five genera is likely a reflection of the biological importance of these structures, warranting further investigation regarding their role in the evolution and possible development of antiviral resistance. The studies herein demonstrate that pathogen genomics-based analytical approaches are useful both for understanding the mechanisms that drive the evolution and spread of rapidly evolving viral pathogens such as orthomyxoviruses, and for illuminating how these approaches could be leveraged to improve the management of these pathogens. DA - 2019 DB - OpenUCT DP - University of Cape Town KW - laboratory sciences LK - https://open.uct.ac.za PY - 2019 T1 - Exploring the phylodynamics, genetic reassortment and RNA secondary structure formation patterns of orthomyxoviruses by comparative sequence analysis TI - Exploring the phylodynamics, genetic reassortment and RNA secondary structure formation patterns of orthomyxoviruses by comparative sequence analysis UR - ER - en_ZA
dc.identifier.urihttps://hdl.handle.net/11427/31729
dc.identifier.vancouvercitationNindo FN. Exploring the phylodynamics, genetic reassortment and RNA secondary structure formation patterns of orthomyxoviruses by comparative sequence analysis. []. ,Faculty of Health Sciences ,Department of Clinical Laboratory Sciences, 2019 [cited yyyy month dd]. Available from: en_ZA
dc.language.rfc3066eng
dc.publisher.departmentDepartment of Clinical Laboratory Sciences
dc.publisher.facultyFaculty of Health Sciences
dc.subjectlaboratory sciences
dc.titleExploring the phylodynamics, genetic reassortment and RNA secondary structure formation patterns of orthomyxoviruses by comparative sequence analysis
dc.typeDoctoral Thesis
dc.type.qualificationlevelDoctoral
dc.type.qualificationnamePhD
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