UBC Theses and Dissertations
Host-virus interactions and the determinants of infection dynamics Byrne, Catherine
With the large global burden of virus-associated diseases, research on viral transmission and pathogenesis is essential. HIV-1, Epstein-Barr virus (EBV), cytomegalovirus (CMV), and SARS-CoV-2 are some of the most ubiquitous infections among global populations, each associated with an enormous disease burden. Using combinations of cohort data, mouse models, and mathematical modelling, we addressed specific questions related to each of these infections. EBV-HIV-1 coinfections correlate with high risks of cancerous malignancies and elevated EBV viral loads in saliva. To discern how HIV-1 exacerbates EBV infection, we analyzed cohort data and developed a mathematical model of the EBV infection dynamics within the tonsils. Our results suggest that coinfected individuals have a weaker EBV-specific immune response and higher rates of B cell reactivation than individuals with only EBV infection, which together explain their higher EBV loads and more frequent shedding in the saliva. CMV is the number one cause of congenital infection. However, no approved vaccine is available in part due to a lack of knowledge on how primary infection becomes established and the determinants of reinfection. Using mathematical and mouse infection models, we examined the dynamics of primary infection and reinfection, determined the drivers of CMV transmission, and tested vaccination strategies. Our results bring insight into the immune correlates of protection and the importance of strain differences in determining the efficiency and severity of reinfection. Further, we show that even modestly-protective vaccines administered to children are likely sufficient for decreasing infection in the population and the burden of congenital CMV. The high transmissibility of SARS-CoV-2 has caused the historic COVID-19 pandemic. Mathematical models have proven essential to predict the spread and impacts of COVID-19. We created a mathematical model of SARS-CoV-2 transmission, focusing on within-household transmission to discern its contribution to the pandemic. We showed that these interactions are essential for determining SARS-CoV-2 spread during times of social distancing and determined what testing strategies can help reveal the true amount of transmission occurring within homes. Together, this work reveals novel insights into the determinants of viral transmission and the within-host dynamics that can help inform future prevention and treatment strategies.
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