What makes a super-spreader? Genetic control, evolutionary constraints and epidemiological implications of heterogeneity in host infectiousness

Identifying the role of host genetics associated with disease resistance in humans and animals has led to important advances in disease control, but there is increasing evidence that individuals not only vary in their resistance to acquire infectious pathogens, but also in infectiousness - their ability to transmit pathogens. The contribution of host genetics to the phenotypic variation in infectiousness is largely unknown for most infectious diseases. An urgent - but elusive - agenda in disease ecology and epidemiology is therefore to identify the genetic drivers of variation in host infectiousness. This proposal will focus on the genetic and immune determinants and evolutionary constraints underlying individual variation in host infectiousness. We will harness the fruit fly Drosophila melanogaster as an established model system of infection, immunity, and behaviour to disentangle the genetic and immune determinants, and evolutionary constraints underlying extreme host heterogeneity in pathogen transmission. We will further enhance these empirical strengths by employing recently developed statistical inference and epidemiological modelling tools which allow quantifying the effect of known host genetic polymorphisms on specific epidemic outcomes. Given the pervasive threat of emerging infectious diseases in human, animal and plant populations, our aims are to produce timely and novel research focusing on the genetic and immune determinants and evolutionary constraints underlying individual variation in host infectiousness: While we know much about genetic variation for some disease-related traits, the contribution of host genetics to infectiousness is generally unknown. A deeper understanding of the relationship between host susceptibility and infectiousness, and their relative contributions in transmission dynamics, is urgently needed to devise and predict the outcome of disease control strategies. Immune-related pathways are well-described in several vertebrate and invertebrate systems, but we have little knowledge of the extent to which immune pathways regulate variation in host infectiousness. Genetic variation is the fuel for evolution, but how host infectiousness is likely to evolve in response to disease control methods is unknown. We propose selection experiments as a powerful approach to uncover evolutionary constraints and trade-offs between host infectiousness and other traits. Our overarching, long-term goal is to achieve both an advance in our fundamental understanding of the role of host heterogeneity in infectious disease, and useful insight into biomarkers for disease control and prevention in animal and human populations. These aims align directly with UKRI’s Strategic Delivery Plan, specifically with the aims of supporting world-class ideas in bioscience discoveries by understanding the rules of life and in achieving world-class impacts, particularly in the integrated understanding of health.