Dissecting genetic and sex-specific sources of host heterogeneity in pathogen shedding and spread

Abstract

Host heterogeneity in disease transmission is widespread but precisely how different host traits drive this heterogeneity remains poorly understood. Part of the difficulty in linking individual variation to population-scale outcomes is that individual hosts can differ on multiple behavioral, physiological and immunological axes, which will together impact their transmission potential. Moreover, we lack well-characterized, empirical systems that enable the quantification of individual variation in key host traits, while also characterizing genetic or sex-based sources of such variation. Here we used Drosophila melanogaster and Drosophila C Virus as a host-pathogen model system to dissect the genetic and sex-specific sources of variation in multiple host traits that are central to pathogen transmission. Our findings show complex interactions between genetic background, sex, and female mating status accounting for a substantial proportion of variance in lifespan following infection, viral load, virus shedding, and viral load at death. Two notable findings include the interaction between genetic background and sex accounting for nearly 20% of the variance in viral load, and genetic background alone accounting for ~10% of the variance in viral shedding and in lifespan following infection. To understand how variation in these traits could generate heterogeneity in individual pathogen transmission potential, we combined measures of lifespan following infection, virus shedding, and previously published data on fly social aggregation. We found that the interaction between genetic background and sex explained ~12% of the variance in individual transmission potential. Our results highlight the importance of characterising the sources of variation in multiple host traits to understand the drivers of heterogeneity in disease transmission.

Dilution effects in disease ecology

“…Underlying the effects of genetic diversity on the transmission of pathogens is intraspecific variation in host quality. Individuals within a species can vary, for example, in their probability of exposure to a pathogen or parasite and their susceptibility to infection (Civitello & Rohr, 2014 ; Dwyer et al, 1997 ; Poulin, 2011 ; Sauer et al, 2019 ; Warburton & Vonhof, 2018 ), their probability of transmitting the pathogen or parasite onwards (Cornet et al, 2014 ; Lloyd‐Smith et al, 2005 ; Pulkkinen & Ebert, 2004 ; Siva‐Jothy & Vale, 2021 ; Stephenson et al, 2017 ; White et al, 2018 ), and their attractiveness to vectors such as aphids or mosquitoes (Bruns et al, 2021 ; Shapiro et al, 2012 ; Yan et al, 2018 ). The combined effect of these factors can be that the majority of pathogens or parasites are transmitted by a small number of individuals, sometimes called ‘superspreaders’ (Lloyd‐Smith et al, 2005 ).…”

Differential gene expression reveals host factors for viral shedding variation in mallards (Anas platyrhynchos) infected with low-pathogenic avian influenza virus

“…Extrinsic host factors linked to heterogeneity in pathogen shedding include food availability (14,15), geographical location (16), toxicant exposure (17), and myriad environmental factors that can affect host immune competence through chronically elevated stress hormones (18). Intrinsic factors linked to pathogen shedding are a host's age (19), sex (20,21), physiology (22)(23)(24), and the immune response (24)(25)(26). In particular, observing how intraspecific variation in pathogen shedding relates to variation in host biological processes can improve our understanding of host factors involved in pathogen transmission.…”

Evolution of pathogen tolerance and emerging infections: A missing experimental paradigm

“…By experimentally imposing long-term selection with the new pathogen B. malayi , we can verify the causal connection between the length of coevolutionary history and the level of host tolerance and parasite evolution. Subsequently, genetic analyses can uncover the mechanistic basis of adaptive changes in host immunity (e.g., possible modulation of costly inflammatory responses; Märkle et al, 2021 ) and pathogen replication and transmission potential ( Siva-Jothy and Vale, 2021 ).…”