Ecology of emerging diseases: virulence and transmissibility of human RNA viruses

Abstract

Emerging infectious diseases continue to represent serious threats to global human health. Novel zoonotic pathogens are continually being recognised, and some ultimately cause significant disease burdens and extensive epidemics. Research and public health initiatives often face emerging pathogens with limited knowledge and resources. Inferences from empirical modelling have begun to uncover the factors determining cross-species transmission and emergence in humans, and subsequently guide risk assessments. However, the dynamics of virulence and transmissibility during the process of emergence are not well understood. Here, I focus on RNA viruses, a priority pathogen type because of their potential for rapid evolution. I use comparative trait-based analyses to investigate how aspects of both host and virus ecology contribute to the risk of virulence and transmissibility within human RNA viruses. To explore these questions, data were collected via systematic literature search protocols. In the first half of this thesis, I focus on viral determinants of virulence and transmissibility. I ask whether virulence can be predicted by viral traits of tissue tropism, transmission route, transmissibility and taxonomic classification. Using a machine learning approach, the most prominent predictors of severe virulence were breadth of tissue tropism, and nonvector-borne transmission routes. When applied to newly reported viruses as test set, the final model predicted disease severity with 87% accuracy. Next, I assess support for hypothesised routes of adaptation during emergence using phylogenetic state-switching models. Propensity for adaptation in small ‘stepwise’ movements versus large ‘off-the-shelf’ jumps differed between virus taxa, though no single route dominated, suggesting multiple independent trajectories of adaptation to human hosts. In addition, phylogenetic regressions showed vector and respiratory-transmitted viruses to be more likely to progress through early stages of emergence. In the second half of this thesis, I focus on how dynamics of virulence and transmissibility differ with respect to nonhuman host diversity, identity, and ecology. Using a regression framework, I observe that viruses with a broader mammalian host range exhibited higher risk of severe virulence, but lower risk of transmissibility, which may reflect potential trade-offs of host specificity. Furthermore, viruses with artiodactyl hosts exhibited lower risk of severe virulence and viruses with bat or nonhuman primate hosts exhibited higher risk of transmissibility. Next, I test hypotheses that mammal species with faster-paced life history may be predisposed to host viruses with greater virulence and transmissibility. Mammal body mass was used as an established proxy for pace of life history. In regression analyses, mammals with faster-paced life history hosted more viruses with severe virulence, though evidence for a relationship with transmissibility was limited. The broad-scale associations presented in this thesis suggest the evolution of virulence and human-to-human transmissibility during zoonotic emergence is a multifactorial, highly dynamic process influenced by both virus and host ecology. Despite this, general characteristics of high-risk emerging viruses are evident. For example, severe virulence was associated with broad niche diversity of both tissue tropisms at the within-host scale, and host species at the macroecological scale. However, risk factors for virulence and human-to-human transmissibility often did not coincide, which may imply an overarching trade-off between these traits. These analyses can contribute to preparedness and direction within public health strategies by identifying likely candidates for high-impact emergence events among previously known and newly discovered human viruses. The inherent connectivity between RNA viruses, their nonhuman hosts and the resulting implications for human health emphasise the holistic nature of emerging diseases and supports the One Health perspective for infectious disease research.