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Applications of sequencing technologies in monitoring the evolution and transmission of viral pathogens

University of British Columbia

Viruses are obligate intracellular parasites, a diverse set of rapidly-evolving pathogens capable of causing severe disease in humans. New approaches to modern medicine have provided viral treatments that improve the clinical status of patients and prevent transmission. Genetic sequencing is a valuable tool in the field of infectious diseases, being used to investigate various properties of infections including host immunity, pathogen characteristics, and evolutionary trends over time. Viral infections are responsible for millions of deaths per year, and persistent as well as emerging viral infections are associated with high morbidity and mortality around the world. Human immunodeficiency virus (HIV), the virus which causes acquired immune deficiency syndrome (AIDS), was responsible for nearly one million AIDS-related deaths in 2018. Although the current paradigm of HIV treatment involves the use of antiretroviral medications, drug resistance affects the potency and efficacy of antiretroviral therapy. Emerging viruses, such as the Zika virus (ZIKV), present additional threats to the global managements of infectious diseases. Prior to ZIKV outbreak in Yap Island in 2007 that resulted in 74 confirmed cases, the ZIKV was associated with small sporadic outbreaks in Africa and Asia. In 2016, there were approximately 400,000-1.3 million confirmed cases of ZIKV infections in Brazil alone, indicating increased geographical range of ZIKV away from previous known regions of infections, with detrimental neurological outcomes. In this thesis, the primary objective is to investigate the utility of current sequencing technologies in monitoring and surveillance of circulating viral pathogens. I discuss the extent to which viral sequencing can be used to examine the evolution and transmission of current and emerging viral pathogens, HIV and ZIKV. The aims are to 1) identify the longitudinal annual prevalence of HIV drug resistance in British Columbia, Canada using Sanger sequencing, 2) evaluate the prevalence and the impact of pretreatment HIV drug resistance on treatment outcome in Mbarara, Uganda using “next-generation” sequencing, and 3) assess the potential utility of “next-generation” sequencing in identifying origins of travel-related ZIKV infections in a proof-of-concept study and examine the changing evolutionary trends of circulating strains of ZIKV.

Thesis/Dissertation

eng

Vancouver : University of British Columbia Library

10.14288/1.0380525

Master of Science - MSc

Medicine, Faculty of; Medicine, Department of

2019-09

Graduate

DSpace