Host physiological phenotype explains pathogen reservoir potential

Control of emerging infectious diseases often hinges on identifying a pathogen reservoir, the source of disease transmission. The potential to function as a pathogen reservoir can be influenced by host lifespan, geographic provenance and phylogeny. Yet, no study has identified factors that causally determine the reservoir potential of diverse host species. We propose the host physiological phenotype hypothesis, which predicts that hosts with short‐lived, poorly defended, nutrient rich and high metabolism tissue have greater values for three epidemiological parameters that determine reservoir potential: host susceptibility to infection, competence to infect vectors and ability to support vector populations. We experimentally tested these predictions using a generalist vectored virus and six wild grass species. Host physiological phenotype explained why hosts differed in all three epidemiological parameters while host lifespan, provenance and phylogeny could not explain host competence. Thus, a single, general axis describing variation in host physiological phenotype may explain reservoir potential.     

Vector host-feeding preferences drive transmission of multi-host pathogens: West Nile virus as a model system

Seasonal epizootics of vector-borne pathogens infecting multiple species are ecologically complex and difficult to forecast. Pathogen transmission potential within the host community is determined by the relative abilities of host species to maintain and transmit the pathogen and by ecological factors influencing contact rates between hosts and vectors. Increasing evidence of strong feeding preferences by a number of vectors suggests that the host community experienced by the pathogen may be very different from the local host community. We developed an empirically informed transmission model for West Nile virus (WNV) in four sites using one vector species (Culex pipiens) and preferred and non-preferred avian hosts. We measured strong feeding preferences for American robins (Turdus migratorius) by Cx. pipiens, quantified as the proportion of Cx. pipiens blood meals from robins in relation to their abundance (feeding index). The model accurately predicted WNV prevalence in Cx. pipiens at three of four sites. Sensitivity analysis revealed feeding preference was the most influential parameter on intensity and timing of peak WNV infection in Cx. pipiens and a threshold feeding index for transmission was identified. Our findings indicate host preference-induced contact heterogeneity is a key mediator of vector-borne pathogen epizootics in multi-species host communities, and should be incorporated into multi-host transmission models.     

Pathogens manipulate the preference of vectors,slowing disease spread in a multi‐host system

The spread of vector‐borne pathogens depends on a complex set of interactions among pathogen, vector, and host. In single‐host systems, pathogens can induce changes in vector preferences for infected vs. healthy hosts. Yet it is unclear if pathogens also induce changes in vector preference among host species, and how changes in vector behaviour alter the ecological dynamics of disease spread. Here, we couple multi‐host preference experiments with a novel model of vector preference general to both single and multi‐host communities. We show that viruliferous aphids exhibit strong preferences for healthy and long‐lived hosts. Coupling experimental results with modelling to account for preference leads to a strong decrease in overall pathogen spread through multi‐host communities due to non‐random sorting of viruliferous vectors between preferred and non‐preferred host species. Our results demonstrate the importance of the interplay between vector behaviour and host diversity as a key mechanism in the spread of vectored‐diseases.     

Characteristics and drivers of plant virus community spatial patterns in US west coast grasslands

The spatial distribution of disease risk caused by multi‐pathogen infections is not frequently characterized, limiting understanding of the drivers of infection and thwarting prediction of future risk in a changing environment. Further complicating this predictive understanding is that interactions among multiple pathogens within a host commonly alter transmission success, infection risk, and disease dynamics. By characterizing spatial patterns of Barley and Cereal Yellow Dwarf Virus (B/CYDV) infections that range from the scale of an individual plant to thousands of neighboring plants, we examined the contributions of spatial processes to the distribution of disease risk. In a two‐year field experiment, we planted grass hosts of B/CYDVs into fertilized plots of US west coast grasslands. We determined how vector‐sharing, environmental conditions and spatial variation in host quality affected spatial patterns of single viruses, pairs of viruses and the whole virus community across out‐planted grass hosts. We found that single viruses and virus communities were spatially random, indicating that infection does not solely spread through the community in a wave‐like manner. On the other hand, we found that pairs of viruses, especially those that share a vector species, were aggregated spatially. This suggests that if within‐host competition exists, it is not strong. Aggregation in one pair of viruses was more frequent due to environmental conditions and spatial variation in out‐planted host quality, measured as vector preference. These results highlight the importance of insect vectors for predicting the spatial distribution of coinfection risk by B/CYDVs.     

Risk of Exposure to Eastern Equine Encephalomyelitis Virus Increases with the Density of Northern Cardinals

For a variety of infectious diseases, the richness of the community of potential host species has emerged as an important factor in pathogen transmission, whereby a higher richness of host species is associated with a lowered disease risk. The proposed mechanism driving this pattern is an increased likelihood in species-rich communities that infectious individuals will encounter dead-end hosts. Mosquito-borne pathogen systems potentially are exceptions to such “dilution effects” because mosquitoes vary their rates of use of vertebrate host species as bloodmeal sources relative to host availabilities. Such preferences may violate basic assumptions underlying the hypothesis of a dilution effect in pathogen systems. Here, we describe development of a model to predict exposure risk of sentinel chickens to eastern equine encephalitis virus (EEEV) in Walton County, Florida between 2009 and 2010 using avian species richness as well as densities of individual host species potentially important to EEEV transmission as candidate predictor variables. We found the highest support for the model that included the density of northern cardinals, a highly preferred host of mosquito vectors of EEEV, as a predictor variable. The highest-ranking model also included Culiseta melanura abundance as a predictor variable. These results suggest that mosquito preferences for vertebrate hosts influence pathogen transmission.     

Ecosystem dynamics, biological diversity and emerging infectious diseases

In this article, we summarize the major scientific developments of the last decade on the transmission of infectious agents in multi-host systems. Almost sixty percent of the pathogens that have emerged in humans during the last 30-40 years are of animal origin and about sixty percent of them show an important variety of host species besides humans (3 or more possible host species). In this review, we focus on zoonotic infections with vector-borne transmission and dissect the contrasting effects that a multiplicity of host reservoirs and vectors can have on their disease dynamics. We discuss the effects exerted by host and vector species richness and composition on pathogen prevalence (i.e., reduction, including the dilution effect, or amplification). We emphasize that, in multiple host systems and for vector-borne zoonotic pathogens, host reservoir species and vector species can exert contrasting effect locally. The outcome on disease dynamics (reduced pathogen prevalence in vectors when the host reservoir species is rich and increased pathogen prevalence when the vector species richness increases) may be highly heterogeneous in both space and time. We then ask briefly how a shift towards a more systemic perspective in the study of emerging infectious diseases, which are driven by a multiplicity of hosts, may stimulate further research developments. Finally, we propose some research avenues that take better into account the multi-host species reality in the transmission of the most important emerging infectious diseases, and, particularly, suggest, as a possible orientation, the careful assessment of the life-history characteristics of hosts and vectors in a community ecology-based perspective.     

Integrating phylogenetic and ecological distances reveals new insights into parasite host specificity

The range of hosts a pathogen infects (host specificity) is a key element of disease risk that may be influenced by both shared phylogenetic history and shared ecological attributes of prospective hosts. Phylospecificity indices quantify host specificity in terms of host relatedness, but can fail to capture ecological attributes that increase susceptibility. For instance, similarity in habitat niche may expose phylogenetically unrelated host species to similar pathogen assemblages. Using a recently proposed method that integrates multiple distances, we assess the relative contributions of host phylogenetic and functional distances to pathogen host specificity (functional–phylogenetic host specificity). We apply this index to a data set of avian malaria parasite (Plasmodium and Haemoproteus spp.) infections from Melanesian birds to show that multihost parasites generally use hosts that are closely related, not hosts with similar habitat niches. We also show that host community phylogenetic ß‐diversity (Pßd) predicts parasite Pßd and that individual host species carry phylogenetically clustered Haemoproteus parasite assemblages. Our findings were robust to phylogenetic uncertainty, and suggest that phylogenetic ancestry of both hosts and parasites plays important roles in driving avian malaria host specificity and community assembly. However, restricting host specificity analyses to either recent or historical timescales identified notable exceptions, including a ‘habitat specialist’ parasite that infects a diversity of unrelated host species with similar habitat niches. This work highlights that integrating ecological and phylogenetic distances provides a powerful approach to better understand drivers of pathogen host specificity and community assembly.     

Fine-scale variation in vector host use and force of infection drive localized patterns of West Nile virus transmission

The influence of host diversity on multi-host pathogen transmission and persistence can be confounded by the large number of species and biological interactions that can characterize many transmission systems. For vector-borne pathogens, the composition of host communities has been hypothesized to affect transmission; however, the specific characteristics of host communities that affect transmission remain largely unknown. We tested the hypothesis that vector host use and force of infection (i.e., the summed number of infectious mosquitoes resulting from feeding upon each vertebrate host within a community of hosts), and not simply host diversity or richness, determine local infection rates of West Nile virus (WNV) in mosquito vectors. In suburban Chicago, Illinois, USA, we estimated community force of infection for West Nile virus using data on Culex pipiens mosquito host selection and WNV vertebrate reservoir competence for each host species in multiple residential and semi-natural study sites. We found host community force of infection interacted with avian diversity to influence WNV infection in Culex mosquitoes across the study area. Two avian species, the American robin (Turdus migratorius) and the house sparrow (Passer domesticus), produced 95.8% of the infectious Cx. pipiens mosquitoes and showed a significant positive association with WNV infection in Culex spp. mosquitoes. Therefore, indices of community structure, such as species diversity or richness, may not be reliable indicators of transmission risk at fine spatial scales in vector-borne disease systems. Rather, robust assessment of local transmission risk should incorporate heterogeneity in vector host feeding and variation in vertebrate reservoir competence at the spatial scale of vector-host interaction.     

Knock‐on community impacts of a novel vector: spillover of emerging DWV‐B from Varroa‐infested honeybees to wild bumblebees

Novel transmission routes can directly impact the evolutionary ecology of infectious diseases, with potentially dramatic effect on host populations and knock‐on effects on the wider host community. The invasion of Varroa destructor, an ectoparasitic viral vector in Western honeybees, provides a unique opportunity to examine how a novel vector affects disease epidemiology in a host community. This specialist honeybee mite vectors deformed wing virus (DWV), an important re‐emerging honeybee pathogen that also infects wild bumblebees. Comparing island honeybee and wild bumblebee populations with and without V. destructor, we show that V. destructor drives DWV prevalence and titre in honeybees and sympatric bumblebees. Viral genotypes are shared across hosts, with the potentially more virulent DWV‐B overtaking DWV‐A in prevalence in a current epidemic. This demonstrates disease emergence across a host community driven by the acquisition of a specialist novel transmission route in one host, with dramatic community level knock‐on effects.     

Vector preference for hosts differing in infection status: sharpshooter movement and Xylella fastidiosa transmission

1. Epidemiological theory predicts that vector preference for hosts differing in infection status (i.e. healthy or infected) affects disease dynamics. 2. Numerous studies have documented strong vector preference for or discrimination against infected hosts. However, the significance of these behaviours for pathogen transmission and spread has been poorly described. 3. We conducted a series of choice assays to evaluate orientation preference, feeding preference, and movement rates of an important group of vectors, the sharpshooter leafhoppers, based on host infection status for the generalist plant pathogen, Xylella fastidiosa Wells et al. 4. Sharpshooters did not discriminate between healthy versus infected‐but‐asymptomatic grapevines, but they oriented preferentially to healthy grapevines more frequently than either symptomatic vines or those artificially coloured to mimic disease symptoms. 5. In a field trial three sharpshooter species showed different movement rates and preferences for feeding site, but all species exhibited similar and significant preference for healthy hosts. 6. Although there was no significant difference in acquisition efficiency among vector species, those individuals that spent more time on healthy hosts tended to be less likely to acquire the pathogen. 7. These results suggest that sharpshooters discriminate against infected grapevines, which are likely to be of poorer quality, with visual cues playing a role in host selection. Preference by these vectors may affect pathogen acquisition, which could affect disease spread in the field.     

Dynamics of Vector-Host Interactions in Avian Communities in Four Eastern Equine Encephalitis Virus Foci in the Northeastern U.S.

Background

Eastern equine encephalitis (EEE) virus (Togaviridae, Alphavirus) is a highly pathogenic mosquito-borne zoonosis that is responsible for occasional outbreaks of severe disease in humans and equines, resulting in high mortality and neurological impairment in most survivors. In the past, human disease outbreaks in the northeastern U.S. have occurred intermittently with no apparent pattern; however, during the last decade we have witnessed recurring annual emergence where EEE virus activity had been historically rare, and expansion into northern New England where the virus had been previously unknown. In the northeastern U.S., EEE virus is maintained in an enzootic cycle involving the ornithophagic mosquito, Culiseta melanura, and wild passerine (perching) birds in freshwater hardwood swamps. However, the identity of key avian species that serve as principal virus reservoir and amplification hosts has not been established. The efficiency with which pathogen transmission occurs within an avian community is largely determined by the relative reservoir competence of each species and by ecological factors that influence contact rates between these avian hosts and mosquito vectors.

Methodology and principle findings

Contacts between vector mosquitoes and potential avian hosts may be directly quantified by analyzing the blood meal contents of field-collected specimens. We used PCR-based molecular methods and direct sequencing of the mitochondrial cytochrome b gene for profiling of blood meals in Cs. melanura, in an effort to quantify its feeding behavior on specific vertebrate hosts, and to infer epidemiologic implications in four historic EEE virus foci in the northeastern U.S. Avian point count surveys were conducted to determine spatiotemporal host community composition. Of 1,127 blood meals successfully identified to species level, >99% of blood meals were from 65 avian hosts in 27 families and 11 orders, and only seven were from mammalian hosts representing three species. We developed an empirically informed mathematical model for EEE virus transmission using Cs. melanura abundance and preferred and non-preferred avian hosts. To our knowledge this is the first mathematical model for EEE virus, a pathogen with many potential hosts, in the northeastern U.S. We measured strong feeding preferences for a number of avian species based on the proportion of mosquito blood meals identified from these bird species in relation to their observed frequencies. These included: American Robin, Tufted Titmouse, Common Grackle, Wood Thrush, Chipping Sparrow, Black-capped Chickadee, Northern Cardinal, and Warbling Vireo. We found that these bird species, most notably Wood Thrush, play a dominant role in supporting EEE virus amplification. It is also noteworthy that the competence of some of the aforementioned avian species for EEE virus has not been established. Our findings indicate that heterogeneity induced by mosquito host preference, is a key mediator of the epizootic transmission of vector-borne pathogens.

Conclusion and significance

Detailed knowledge of the vector-host interactions of mosquito populations in nature is essential for evaluating their vectorial capacity and for assessing the role of individual vertebrates as reservoir hosts involved in the maintenance and amplification of zoonotic agents of human diseases. Our study clarifies the host associations of Cs. melanura in four EEE virus foci in the northeastern U.S., identifies vector host preferences as the most important transmission parameter, and quantifies the contribution of preference-induced contact heterogeneity to enzootic transmission. Our study identifies Wood Thrush, American Robin and a few avian species that may serve as superspreaders of EEE virus. Our study elucidates spatiotemporal host species utilization by Cs. melanura in relation to avian host community. This research provides a basis to better understand the involvement of Cs. melanura and avian hosts in the transmission and ecology of EEE virus and the risk of human infection in virus foci.     

ROLE OF EVOLVED HOST BREADTH IN THE INITIAL EMERGENCE OF AN RNA VIRUS

Understanding how evolution promotes pathogen emergence would aid disease management, and prediction of future host shifts. Increased pathogen infectiousness of different hosts may occur through direct selection, or fortuitously via indirect selection. However, it is unclear which type of selection tends to produce host breadth promoting pathogen emergence. We predicted that direct selection for host breadth should foster emergence by causing higher population growth on new hosts, lower among‐population variance in growth on new hosts, and lower population variance in growth across new hosts. We tested the predictions using experimentally evolved vesicular stomatitis virus populations, containing groups of host‐use specialists, directly selected generalists, and indirectly selected generalists. In novel‐host challenges, viruses directly selected for generalism showed relatively higher or equivalent host growth, lower among‐population variance in host growth, and lower population variance in growth across hosts. Thus, two of three outcomes supported our prediction that directly selected host breadth should favor host colonization. Also, we observed that indirectly selected generalists were advantaged over specialist viruses, indicating that fortuitous changes in host breadth may also promote emergence. We discuss evolution of phenotypic plasticity versus environmental robustness in viruses, virus avoidance of extinction, and surveillance of pathogen niche breadth to predict future likelihood of emergence.     

A field test of the dilution effect hypothesis in four avian multi-host pathogens

The Dilution Effect Hypothesis (DEH) argues that greater biodiversity lowers the risk of disease and reduces the rates of pathogen transmission since more diverse communities harbour fewer competent hosts for any given pathogen, thereby reducing host exposure to the pathogen. DEH is expected to operate most intensely in vector-borne pathogens and when species-rich communities are not associated with increased host density. Overall, dilution will occur if greater species diversity leads to a lower contact rate between infected vectors and susceptible hosts, and between infected hosts and susceptible vectors. Field-based tests simultaneously analysing the prevalence of several multi-host pathogens in relation to host and vector diversity are required to validate DEH. We tested the relationship between the prevalence in house sparrows (Passer domesticus) of four vector-borne pathogens–three avian haemosporidians (including the avian malaria parasite Plasmodium and the malaria-like parasites Haemoproteus and Leucocytozoon) and West Nile virus (WNV)–and vertebrate diversity. Birds were sampled at 45 localities in SW Spain for which extensive data on vector (mosquitoes) and vertebrate communities exist. Vertebrate censuses were conducted to quantify avian and mammal density, species richness and evenness. Contrary to the predictions of DEH, WNV seroprevalence and haemosporidian prevalence were not negatively associated with either vertebrate species richness or evenness. Indeed, the opposite pattern was found, with positive relationships between avian species richness and WNV seroprevalence, and Leucocytozoon prevalence being detected. When vector (mosquito) richness and evenness were incorporated into the models, all the previous associations between WNV prevalence and the vertebrate community variables remained unchanged. No significant association was found for Plasmodium prevalence and vertebrate community variables in any of the models tested. Despite the studied system having several characteristics that should favour the dilution effect (i.e., vector-borne pathogens, an area where vector and host densities are unrelated, and where host richness is not associated with an increase in host density), none of the relationships between host species diversity and species richness, and pathogen prevalence supported DEH and, in fact, amplification was found for three of the four pathogens tested. Consequently, the range of pathogens and communities studied needs to be broadened if we are to understand the ecological factors that favour dilution and how often these conditions occur in nature.     

Spatiotemporal Model of Barley and Cereal Yellow Dwarf Virus Transmission Dynamics with Seasonality and Plant Competition

Many generalist pathogens are influenced by the spatial distributions and relative abundances of susceptible host species. The spatial structure of host populations can influence patterns of infection incidence (or disease outbreaks), and the effects of a generalist pathogen on host community dynamics in a spatially heterogeneous community may differ from predictions derived via simple models. In this paper, we model the transmission of a generalist pathogen within a patch framework that incorporates the movement of vectors between discrete host patches to investigate the effects of local host community composition and vector movement rates on disease dynamics.     

Pliant pathogens: Estimating viral spread when confronted with new vector,host, and environmental conditions

1. Pathogen spread rates are determined, in part, by the performance of pathogens under altered environmental conditions and their ability to persist while switching among hosts and vectors.
2. To determine the effects of new conditions (host, vector, and nutrient) on pathogen spread rate, we introduced a vector‐borne viral plant pathogen, Barley Yellow Dwarf Virus PAV (BYDV‐PAV) into hosts, vectors, and host nutrient supplies that it had not encountered for thousands of viral generations. We quantified pathogen prevalence over the course of two serial inoculations under the new conditions. Using individual‐level transmission rates from this experiment, we parameterized a dynamical model of disease spread and projected spread across host populations through a growing season.
3. A change in nutrient conditions (increased supply of phosphorus) reduced viral transmission whereas shifting to a new vector or host species had no effect on infection prevalence. However, the reduction in the new nutrient environment was only temporary; infection prevalence recovered after the second inoculation.
4. Synthesis. These results highlight how robust the pathogen, BYDV‐PAV, is to changes in its biotic and abiotic environment. Our study also highlights the need to quantify longitudinal infection information beyond snapshot assessments to project disease risk for pathogens in new environments.

     

Heterogeneity of Rift Valley fever virus transmission potential across livestock hosts,quantified through a model-based analysis of host viral load and vector infection

Quantifying the variation of pathogens’ life history traits in multiple host systems is crucial to understand their transmission dynamics. It is particularly important for arthropod-borne viruses (arboviruses), which are prone to infecting several species of vertebrate hosts. Here, we focus on how host-pathogen interactions determine the ability of host species to transmit a virus to susceptible vectors upon a potentially infectious contact. Rift Valley fever (RVF) is a viral, vector-borne, zoonotic disease, chosen as a case study. The relative contributions of livestock species to RVFV transmission has not been previously quantified. To estimate their potential to transmit the virus over the course of their infection, we 1) fitted a within-host model to viral RNA and infectious virus measures, obtained daily from infected lambs, calves, and young goats, 2) estimated the relationship between vertebrate host infectious titers and probability to infect mosquitoes, and 3) estimated the net infectiousness of each host species over the duration of their infectious periods, taking into account different survival outcomes for lambs. Our results indicate that the efficiency of viral replication, along with the lifespan of infectious particles, could be sources of heterogeneity between hosts. Given available data on RVFV competent vectors, we found that, for similar infectious titers, infection rates in the Aedes genus were on average higher than in the Culex genus. Consequently, for Aedes-mediated infections, we estimated the net infectiousness of lambs to be 2.93 (median) and 3.65 times higher than that of calves and goats, respectively. In lambs, we estimated the overall infectiousness to be 1.93 times higher in individuals which eventually died from the infection than in those recovering. Beyond infectiousness, the relative contributions of host species to transmission depend on local ecological factors, including relative abundances and vector host-feeding preferences. Quantifying these contributions will ultimately help design efficient, targeted, surveillance and vaccination strategies.     

From one host to another: tracking vector movements using microsatellite markers

In principle, the solution to stopping the spread of any vectorborne pathogen is a simple one – just stop infected vectors from biting new hosts and the pathogen cannot spread. Importantly, this does not necessarily require killing all vectors, or protecting all hosts. Transmission only occurs when an infected vector moves to a new host, and so knowing how vectors move between hosts in nature and how they choose hosts is crucial to understanding transmission. For example, the infection status of a potential vector or that of a potential host would have a huge influence on pathogen transmission if it affected vector movement or host choice. Remarkably little is known about how vectors move between and choose hosts in nature, in part because of the logistical difficulties of tracking vector movement. This is why the article by Levin and Parker ( 2014 ) in this issue of Molecular Ecology is so exciting.     

Decreased small mammal and on-host tick abundance in association with invasive red imported fire ants (Solenopsis invicta)

Invasive species may impact pathogen transmission by altering the distributions and interactions among native vertebrate reservoir hosts and arthropod vectors. Here, we examined the direct and indirect effects of the red imported fire ant (Solenopsis invicta) on the native tick, small mammal and pathogen community in southeast Texas. Using a replicated large-scale field manipulation study, we show that small mammals were more abundant on treatment plots where S. invicta populations were experimentally reduced. Our analysis of ticks on small mammal hosts demonstrated a threefold increase in the ticks caught per unit effort on treatment relative to control plots, and elevated tick loads (a 27-fold increase) on one common rodent species. We detected only one known human pathogen (Rickettsia parkeri), present in 1.4% of larvae and 6.7% of nymph on-host Amblyomma maculatum samples but with no significant difference between treatment and control plots. Given that host and vector population dynamics are key drivers of pathogen transmission, the reduced small mammal and tick abundance associated with S. invicta may alter pathogen transmission dynamics over broader spatial scales.     

Vector preference and host defense against infection interact to determine disease dynamics

Vector preference based on host infection status has long been recognized for its importance in disease dynamics. Prior theoretical work has assumed that all hosts are uniformly susceptible to the pathogen. Here we investigated disease dynamics when this assumption is relaxed using a series of vector–host epidemiological compartment models with variable levels of host resistance or tolerance to infection – collectively termed defense. In our models, vectors cannot acquire the infection from resistant hosts but can acquire from tolerant hosts. Specifically, we investigated the interacting effects of vector preference and host defense in a series of single‐ and two‐patch models. Results indicate that resistant host types generally reduce disease prevalence and pathogen spillover, independent of vector preference. The epidemiological consequences of host tolerance, however, depended on vector preference. When vectors preferred diseased hosts, tolerance reduced incidence compared to susceptible hosts; when vectors avoided diseased hosts, tolerance enhanced disease prevalence. Finally, a variation of the model that included preference‐based vector patch leaving rates suggests that both resistance and tolerance can promote pathogen spillover if vectors prefer diseased hosts, because of increased vector dispersal into susceptible patches. Collectively, we found complex, context‐dependent effects of vector preference and host defense on disease dynamics. In the context of management programs for vector‐borne diseases, managers should consider both the precise form of host defense present in a population, breed, or cultivar, as well as vector feeding behavior.     

Serial infection of diverse host (Mus) genotypes rapidly impedes pathogen fitness and virulence

Reduced genetic variation among hosts may favour the emergence of virulent infectious diseases by enhancing pathogen replication and its associated virulence due to adaptation to a limited set of host genotypes. Here, we test this hypothesis using experimental evolution of a mouse-specific retroviral pathogen, Friend virus (FV) complex. We demonstrate rapid fitness (i.e. viral titre) and virulence increases when FV complex serially infects a series of inbred mice representing the same genotype, but not when infecting a diverse array of inbred mouse strains modelling the diversity in natural host populations. Additionally, a single infection of a different host genotype was sufficient to constrain the emergence of a high fitness/high virulence FV complex phenotype in these experiments. The potent inhibition of viral fitness and virulence was associated with an observed loss of the defective retroviral genome (spleen focus-forming virus), whose presence exacerbates infection and drives disease in susceptible mice. Results from our experiments provide an important first step in understanding how genetic variation among vertebrate hosts influences pathogen evolution and suggests that serial exposure to different genotypes within a single host species may act as a constraint on pathogen adaptation that prohibits the emergence of more virulent infections. From a practical perspective, these results have implications for low-diversity host populations such as endangered species and domestic animals.