Biology subjects

Hawley, D. M.

Publications and source records attributed to Hawley, D. M..

4 recordsLinked to original sources

bioRxiv2025

Host prior exposure augments heterogeneity in gene expression in both host and pathogen during in vivo infection

Variability in acquired protection, whether from prior pathogen exposure or vaccination, is increasingly recognized as a key determinant of host population-level variation in disease traits. It remains unclear whether this extends to the within-host physiological environment and what the consequences are for reinfecting pathogens. Here, we asked whether prior pathogen exposure of hosts induces gene expression heterogeneity in the host and/or pathogen during infection. We quantified gene expression in vivo following high-dose pathogen challenge of house finches (Haemorhous mexicanus) previously given controlled, varied exposure histories to a bacterial pathogen (Mycoplasma gallisepticum; MG). To measure gene expression heterogeneity, we collected transcriptomic data from two host tissues (conjunctiva and spleen), and, simultaneously, from pathogen infecting the primary site of infection (conjunctiva). In the conjunctiva, but not the spleen, prior pathogen exposure induced significant heterogeneity in host gene expression relative to pathogen-naive hosts. Further, hosts that received a lower prior exposure dose rather than a higher primary dose showed the greatest within-group heterogeneity in expression during re-challenge. Functional enrichment analyses for significantly variable host genes indicated an over-representation of terms involved in the immune systems response to pathogens, namely a diversified inflammatory response, in birds with prior pathogen exposure. The infecting pathogen from the conjunctiva followed similar patterns of heterogeneity in host gene expression, where pathogen infecting hosts with prior exposure had more heterogeneous expression than those infecting pathogen-naive hosts. While the exact mechanisms that underlie greater variation in gene expression cannot be resolved by this study, our results are consistent with the hypothesis that prior host exposure induces a within-host environment that promotes heterogeneous gene expression across both hosts and pathogens. This suggests that to understand the coevolutionary dynamics of infectious diseases we must consider not only the genetic sequence variation, but also gene expression variation in host and pathogen.

ecology↗

bioRxiv2025

Infected host competence overshadows heterogeneity in susceptibility in shaping experimental epizootics

The accelerated rate of disease emergence in recent decades underscores the need to understand conditions that promote or dampen epidemics. Theoretical models consistently show that epidemics are smaller in populations with higher among-individual heterogeneity in susceptibility. Experimental tests of these predictions are rare but critical for understanding how heterogeneity in susceptibility shapes epidemics in natural systems. We directly link data-parameterized models from previous dose response experiments in the house finch and Mycoplasma gallisepticum system to experimental epidemics in replicated aviary mesocosm flocks. We manipulated flock-level heterogeneity in susceptibility by seeding epidemics in flocks composed of either pathogen-naive or previously exposed birds, which prior work showed have higher heterogeneity in susceptibility relative to pathogen-naive populations. We tracked epidemics for over two months, combining empirical data and stochastic compartmental models to address how heterogeneity in susceptibility changes epidemic severity. Consistent with previous work, estimates of heterogeneity in susceptibility based on coefficients of variation were higher for flocks given prior pathogen exposure relative to pathogen-naive flocks. However, in contrast with prior work on individually-housed birds which showed relatively homogeneous susceptibility for pathogen-naive birds, the pathogen-naive flocks in this study were better described by heterogeneous, rather than homogenous, models of susceptibility. This suggests that flock-level epidemics captured sources of heterogeneity absent in controlled experiments, such as transmission heterogeneity. Finally, although prior exposure conferred protection from disease at the individual level, we did not detect predicted effects of prior exposure and its associated flock-level heterogeneity on prevalence. However, our ability to detect effects of prior exposure on flock-level prevalence was obscured by unexpected variation in the competence of the initially pathogen-naive index birds that seeded each epidemic. This variation in infectiousness among index birds significantly predicted flock-level prevalence, with low index bird infectiousness contributing to the absence of detectable epidemics in two of the three naive flocks. Our stochastic simulations generated a wide range of prevalence outcomes for small epidemics over the timescales examined, further underscoring the challenges of measuring transmission dynamics in naturalistic settings, where unexpected variation in host traits such as competence can obscure other factors of interest. Open research statementData are not yet provided. Data and code will be permanently and publicly archived in the Virginia Tech Data Repository if the paper is accepted for publication

ecology↗

bioRxiv2024

Pathogen priming alters host transmission potential and predictors of transmissibility in a wild songbird species

Pathogen reinfections occur widely, but the extent to which reinfected hosts contribute to ongoing transmission is often unknown despite its implications for host-pathogen dynamics. House finches (Haemorhous mexicanus) acquire partial protection from initial exposure to the bacterial pathogen Mycoplasma gallisepticum (MG), with hosts readily reinfected with homologous or heterologous strains on short timescales. However, the extent to which reinfected hosts contribute to MG transmission has not been tested. We used three pathogen priming treatments- none, intermediate (repeated low-dose priming), or high (single high-dose priming)- to test how prior pathogen priming alters the likelihood of transmission to a cagemate during index bird reinfection with a homologous or heterologous MG strain. Relative to unprimed control hosts, the highest priming level strongly reduced maximum pathogen loads and transmission success of index birds during reinfections. Reinfections with the heterologous strain, previously shown to be more virulent and transmissible than the homologous strain used, resulted in higher pathogen loads within high-primed index birds, and showed higher overall transmission success regardless of host priming treatment. This suggests that inherent differences in strain transmissibility are maintained in primed hosts, leading to the potential for ongoing transmission during reinfections. Finally, among individuals, transmission was most likely from hosts harboring higher within-host pathogen loads, while associations between disease severity and transmission probability were dependent on a given birds priming treatment. Overall, our results indicate that reinfections can result in ongoing transmission, particularly where reinfections result from heterologous and highly transmissible strains, with key implications for virulence evolution. ImportanceAs Covid-19 dramatically illustrated, humans and other animals can become infected with the same pathogen multiple times. Because individuals already have defenses against pathogen their immune systems have encountered before, reinfections are typically less severe, and are thought to be less contagious, but this is rarely directly tested. We used a songbird species and two strains of its common bacterial pathogen to study how contagious hosts are when their immune systems have some degree of prior experience with a pathogen. We found that reinfected hosts are not as contagious as initially infected ones. However, the more transmissible of the two strains, which also causes more harm to its hosts, was able to multiply more readily than the other strain within reinfected hosts, and was more contagious in both reinfected and first-infected hosts. This suggests that reinfections might favor more harmful pathogen strains that are better able to overcome immune defenses.

evolutionary biology↗

bioRxiv2024

Prior exposure to pathogens augments host heterogeneity in susceptibility and has key epidemiological consequences

Pathogen epidemics are key threats to human and wildlife health. Across systems, host protection from pathogens following initial exposure is often incomplete, resulting in recurrent epidemics through partially-immune hosts. Variation in population-level protection has important consequences for epidemic dynamics, but how acquired protection influences inter{-}individual heterogeneity in susceptibility and its epidemiological consequences remains understudied. We experimentally investigated whether prior exposure (none, low-dose, or high{-}dose) to a bacterial pathogen alters host heterogeneity in susceptibility among songbirds. Hosts with no prior pathogen exposure had little variation in protection, but heterogeneity in susceptibility was significantly augmented by prior pathogen exposure, with the highest variability detected in hosts given high-dose prior exposure. An epidemiological model parameterized with experimental data found that heterogeneity in susceptibility from prior exposure more than halved epidemic sizes compared with a homogeneous population with identical mean protection. However, because infection-induced mortality was also greatly reduced in hosts with prior pathogen exposure, reductions in epidemic size were smaller than expected in hosts with prior exposure. These results highlight the importance of variable protection from prior exposure and/or vaccination in driving population-level heterogeneity and epidemiological dynamics.

microbiology↗