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Becker, D. J.

Publications and source records attributed to Becker, D. J..

33 records · Page 2Linked to original sources

Data proliferation, reconciliation, and synthesis in viral ecology

The fields of viral ecology and evolution have rapidly expanded in the last two decades, driven by technological improvements, and motivated by efforts to discover potentially zoonotic wildlife viruses under the rubric of pandemic prevention. One consequence has been a massive proliferation of host-virus association data, which comprise the backbone of research in viral macroecology and zoonotic risk prediction. These data remain fragmented across numerous data portals and projects, each with their own scope, structure, and reporting standards. Here, we propose that synthesis of host-virus association data is a central challenge to improve our understanding of the global virome and develop foundational theory in viral ecology. To illustrate this, we build an open reconciled mammal-virus database from four key published datasets, applying a standardized taxonomy and metadata. We show that reconciling these datasets provides a substantially richer view of the mammal virome than that offered by any one individual database. We argue for a shift in best practice towards the incremental development and use of synthetic datasets in viral ecology research, both to improve comparability and replicability across studies, and to facilitate future efforts to use machine learning to predict the structure and dynamics of the global virome.

ecology↗

Viral competence data improves rodent reservoir predictions for American orthohantaviruses

Identifying reservoir host species is crucial for understanding the risk of pathogen spillover from wildlife to people. Orthohantaviruses are zoonotic pathogens primarily carried by rodents that cause the diseases hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS) in humans. Given their diversity and abundance, many orthohantaviruses are expected to be undiscovered, and several host relationships remain unclear, particularly in the Americas. Despite the increasing use of predictive models for understanding zoonotic reservoirs, explicit comparisons between different evidence types for demonstrating host associations, and relevance to model performance in applied settings, have not been previously made. Using multiple machine learning methods, we identified phylogenetic patterns in and predicted unidentified reservoir hosts of New World orthohantaviruses based on evidence of infection (RT-PCR data) and competence (live virus isolation data). Infection data were driven by phylogeny, unlike competence data, and boosted regression tree (BRT) models using competence data displayed higher accuracy and a narrower list of predicted reservoirs than those using infection data. Eight species were identified by both BRT models as likely orthohantavirus hosts, with a total of 98 species identified by our infection models and 14 species identified by our competence models. Hosts predicted by competence models are concentrated in the northeastern United States (particularly Myodes gapperi and Reithrodontomys megalotis) and northern South America (several members of tribe Oryzomyini) and should be key targets for empirical monitoring. More broadly, these results demonstrate the value of infection competence data for predictive models of zoonotic pathogen hosts, which can be applied across a range of settings and host-pathogen systems. Author SummaryHuman diseases with wildlife origins constitute a significant risk for human health. Orthohantaviruses are viruses found primarily in rodents that cause disease with high rates of mortality and other complications in humans. An important step in disease prevention is to identify which rodent species carry and transmit orthohantaviruses. By incorporating species relatedness and evidence of different levels of host capacity to be infected and transmit virus, we used predictive modeling to determine unidentified rodent hosts of orthohantaviruses. Models using host competence data outperformed models using host infection data, highlighting the importance of stronger data in model optimization. Our results highlighted roughly a dozen key target species to be monitored that are concentrated in two geographic regions--northeastern United States and northern South America. More broadly, the approaches used in this study can be applied to a variety of other host-pathogen systems that threaten public health.

ecology↗

Urban-adapted mammal species have more known pathogens

The world is rapidly urbanising, inviting mounting concern that urban environments will experience increased zoonotic disease risk. Urban animals could have more frequent contact with humans, and therefore may transmit more zoonotic parasites; however, these animals have a specific set of underlying traits that may determine their parasite burdens while predisposing them to urban living, and they may be subject to more intense research effort, both of which could complicate our ability to reliably identify the role of urbanisation in driving zoonotic risk. Here, we test whether urban mammal species host more known zoonotic parasites, investigating the potential underlying drivers while accounting for a correlated suite of phenotypic, taxonomic, and geographic predictors. We found that urban-adapted mammals have more documented parasites, and more zoonotic parasites specifically: despite comprising only 157 of the 2792 investigated species (6%), urban mammals provided 39% of known host-parasite combinations and showed consistently higher viral discovery rates throughout the last century. However, contrary to predictions, much of the observed effect was attributable to research effort rather than to urban adaptation status itself, and urban-adapted species in fact hosted fewer zoonoses than expected given their total observed parasite richness. We conclude that extended historical contact with humans has had a limited impact on the number of observed zoonotic parasites in urban-adapted mammals; instead, their greater observed zoonotic richness likely reflects sampling bias arising from proximity to humans, which supports a near-universal underlying pattern of conflation between zoonotic risk, research effort, and synanthropy. These findings underscore the need to resolve the ecological mechanisms underlying links between anthropogenic change, sampling bias, and observed wildlife disease dynamics.

ecology↗

Body size affects immune cell proportions in birds and non-volant mammals, but not bats

Powered flight has evolved several times in vertebrates and constrains morphology and physiology in ways that likely have shaped how organisms cope with infections. Some of these constraints likely have impacts on aspects of immunology, such that larger fliers might prioritize risk reduction and safety. Addressing how the evolution of flight may have driven relationships between body size and immunity could be particularly informative for understanding the propensity of some taxa to harbor many virulent and sometimes zoonotic pathogens without showing clinical disease. Here, we used a scaling framework to quantify scaling relationships between body mass and the proportions of two types of white blood cells--lymphocytes, and granulocytes (neutr-/heterophils)--across 60 bat species, 414 bird species, and 256 non-volant mammal species. By using phylogenetically-informed statistical models on field-collected data from wild Neotropical bats, data gleaned from other wild bats available in the literature, and data from captive non-volant mammals and birds, we show that lymphocyte and neutrophil proportions do not vary systematically with body mass among bats. In contrast, larger birds and non-volant mammals have disproportionately higher granulocyte proportions than expected for their body size. Future comparative studies of wild bats, birds, and non-volant mammals of similar body mass should aim to further differentiate evolutionary effects and other aspects of life history on immune defense. Summary statementPowered flight might constrain morphology such that certain immunological features are prioritized. We show that bats largely have similar cell proportions across body mass compared to strong allometric scaling relationships in birds and non-flying mammals.

physiology↗

Surveying the vampire bat (Desmodus rotundus) serum proteome: a resource for identifying immunological proteins and detecting pathogens

Bats are increasingly studied as model systems for longevity and as natural hosts for some virulent viruses. Yet our ability to characterize immune mechanisms of viral tolerance and to quantify infection dynamics in wild bats is often limited by small sample volumes and few species-specific reagents. Here, we demonstrate how proteomics can overcome these limitations by using data-independent acquisition-based shotgun proteomics to survey the serum proteome of 17 vampire bats (Desmodus rotundus) from Belize. Using just 2 L of sample and relatively short separations of undepleted serum digests, we identified 361 proteins across five orders of magnitude. Data are available via ProteomeXchange with identifier PXD022885. Levels of immunological proteins in vampire bat serum were then compared to human plasma via published databases. Of particular interest were anti-viral and anti-bacterial components, circulating 20S proteasome complex, and proteins involved in redox activity; whether any results are specific to vampire bats could be assessed by future pan-mammalian analyses. Lastly, we used known virus proteomes to identify Rh186 from Macacine herpesvirus 3 and ORF1a from Middle East respiratory syndrome-related coronavirus, indicating that mass spectrometry-based techniques show promise for pathogen detection. Overall, these results can be used to design targeted mass-spectrometry assays to quantify immunological markers and detect pathogens. More broadly, our findings also highlight the application of proteomics in advancing wildlife immunology and pathogen surveillance.

molecular biology↗

Unraveling molecular mechanisms of immunity and cancer-resistance using the genomes of the Neotropical bats Artibeus jamaicensis and Pteronotus mesoamericanus

Bats are exceptional among mammals for their powered flight, extended lifespans, and robust immune systems. To investigate the genomic underpinnings of unique bat adaptations, we sequenced the genomes of the Jamaican fruit bat (Artibeus jamaicensis) and the Mesoamerican mustached bat (Pteronotus mesoamericanus) and compared them to a diverse collection of 13 additional bat species together with other mammals. We used the Oxford Nanopore Technologies long-read platform to generate highly complete assemblies (N50: 28-29Mb) and facilitate analysis of complex genomic regions containing duplicated genes. Using gene family size analysis, we found that the type I interferon locus was contracted by eight genes in the most recent common ancestor (MRCA) of bats, shifting the proportion of interferon-{omega} to interferon- and making interferon-{omega} the most common type I interferon in bats. Antiviral genes stimulated by type I interferons were also rapidly evolving, with interferon-induced transmembrane genes experiencing a lineage-specific duplication and strong positive selection in the gene IFIT2. Moreover, the lineage of phyllostomid bats showed an unprecedented expansion of PRDM9, a recombination-related gene also involved in infection responses, raising the possibility that this gene contributes to bat antiviral defenses. These modifications in the bat innate immune system may be important adaptations allowing them to harbor viruses asymptomatically. We additionally found evidence of positive selection on the branch leading to the MRCA of bats acting on 33 tumor suppressors and six DNA repair genes, which may contribute to the low cancer rates and longevity observed across bats. These new genomic resources enable insights into the extraordinary adaptations of bats, with implications for mammalian evolutionary studies and public health.

genomics↗

Temporal patterns of vampire bat rabies and host connectivity in Belize

In the Neotropics, vampire bats (Desmodus rotundus) are the main reservoir host for rabies, a highly fatal encephalitis caused by viruses in the genus Lyssavirus. Although patterns of rabies virus exposure and infection have been well-studied for vampire bats in South America and Mexico, exploring the ecology of vampire bat rabies in other regions is crucial for predicting risks to livestock and humans. In Belize, rabies outbreaks in livestock have increased in recent years, underscoring the need for systematic data on viral dynamics in vampire bats. In this study, we examine the first three years of a longitudinal study on the ecology of vampire bat rabies in northern Belize. Rabies seroprevalence in bats was high across years (29-80%), suggesting active and endemic virus circulation. Across two locations, the seroprevalence time series per site were inversely related and out of phase by at least a year. Microsatellite data demonstrated historic panmixia of vampire bats, and mark-recapture detected rare but contemporary inter-site dispersal. This degree of movement could facilitate spatial spread of rabies virus but is likely insufficient to synchronize infection dynamics, which offers one explanation for the observed phase lag in seroprevalence. More broadly, our analyses suggest frequent transmission of rabies virus within and among vampire bat roosts in northern Belize and highlight the need for future spatiotemporal, phylogenetic, and ecological studies of vampire bat rabies in Central America.

ecology↗

Artificial light at night amplifies seasonal relapse of haemosporidian parasites in a widespread songbird

Urban habitats can shape interactions between hosts and parasites by altering not only exposure rates but also within-host processes. Artificial light at night is common in urban environments, and chronic exposure can impair host immunity in ways that may increase infection. However, studies of causal links between this stressor, immunity, and infection dynamics are rare, particularly in migratory animals. Here, we experimentally tested how artificial light at night affects cellular immunity and haemosporidian parasite intensity across the annual cycle of migrant and resident subspecies of the dark-eyed junco (Junco hyemalis). We monitored an experimental group exposed to light at night and a control group under natural light/dark cycles as they passed through short days simulating early spring to longer days simulating the breeding season, followed by fall migration. Using generalized additive models, we show that artificial light at night increased inflammation, and leukocyte counts were greatest in early spring and fall. At the start of the experiment, few birds had active infections based on microscopy, but PCR revealed many birds had chronic infections. Artificial light at night increased parasitemia across the annual cycle, with strong peaks in spring and fall that were largely absent in control birds. As birds were kept in indoor aviaries to prevent vector exposure, this increased parasitemia indicates relapse of chronic infection during costly life history stages (i.e., reproduction). Although the immunological and parasitological time series were in phase for control birds, cross-correlation analyses also revealed artificial light at night desynchronized leukocyte profiles and parasitemia, which could suggest a general exaggerated inflammatory response. Our study shows how a common anthropogenic influence can shape within-host processes to affect infection dynamics.

ecology↗

Reactivation of latent infections with migration shapes population-level disease dynamics

Annual migration is common across animal taxa and can dramatically shape the spatial and temporal patterns of infectious disease. Although migration can decrease infection prevalence in some contexts, these energetically costly long-distance movements can also have immunosuppressive effects that may interact with transmission processes in complex ways. Here we develop a mechanistic model for the reactivation of latent infections driven by physiological changes or energetic costs associated with migration (i.e., "migratory relapse") and its effects on disease dynamics. We determine conditions under which migratory relapse can amplify or reduce infection prevalence across pathogen and host traits (e.g., infectious periods, virulence, overwinter survival, timing of relapse) and transmission phenologies. We show that relapse at either the start or end of migration can dramatically increase prevalence across the annual cycle and may be crucial for maintaining pathogens with low transmissibility and short infectious periods in migratory populations. Conversely, relapse at the start of migration can reduce the prevalence of highly virulent pathogens by amplifying culling of infected hosts during costly migration, especially for highly transmissible pathogens and those transmitted during migration or the breeding season. Our study provides a mechanistic foundation for understanding the spatiotemporal patterns of relapsing infections in migratory hosts, with implications for zoonotic surveillance and understanding how infection patterns will respond to shifts in migratory propensity associated with environmental change. Further, our work suggests incorporating within-host processes into population-level models of pathogen transmission may be crucial for reconciling the range of migration-infection relationships observed across migratory species.

ecology↗

Predicting the presence and titer of rabies virus neutralizing antibodies from low-volume serum samples in low-containment facilities

Serology is a core component of the surveillance and management of viral zoonoses. Virus neutralization tests are a gold standard serological diagnostic, but requirements for large volumes of serum and high biosafety containment can limit widespread use. Here, focusing on Rabies lyssavirus, a globally important zoonosis, we developed a pseudotype micro-neutralization rapid fluorescent focus inhibition test (pmRFFIT) that overcomes these limitations. Specifically, we adapted an existing micro-neutralization test to use a green fluorescent protein-tagged murine leukemia virus pseudotype in lieu of pathogenic rabies virus, reducing the need for specialized reagents for antigen detection and enabling use in low-containment laboratories. We further used statistical analysis to generate rapid, quantitative predictions of the probability and titer of rabies virus neutralizing antibodies from microscopic imaging of neutralization outcomes. Using 47 serum samples from domestic dogs with neutralizing antibody titers estimated using the fluorescent antibody virus neutralization test (FAVN), pmRFFIT showed moderate sensitivity (78.79%) and high specificity (84.62%). Despite small conflicts, titer predictions were correlated across tests repeated on different dates both for dog samples (r = 0.93), and for a second dataset of sera from wild common vampire bats (r = 0.72, N = 41), indicating repeatability. Our test uses a starting volume of 3.5 L of serum, estimates titers from a single dilution of serum rather than requiring multiple dilutions and end point titration, and may be adapted to target neutralizing antibodies against alternative lyssavirus species. The pmRFFIT enables high-throughput detection of rabies virus neutralizing antibodies in low-biocontainment settings and is suited to studies in wild or captive animals where large serum volumes cannot be obtained.

immunology↗

The macroecology and evolution of avian competence for Borrelia burgdorferi

AimPredicting novel reservoirs of zoonotic pathogens would be improved by identifying inter-specific drivers of host competence, the ability to transmit pathogens to new hosts or vectors. Tick-borne pathogens can provide a useful model system, as larvae become infected only when feeding on a competent host during their first bloodmeal. For tick-borne diseases, competence has been best studied for Borrelia burgdorferi sensu lato (Bbsl), which causes Lyme borreliosis. Major reservoirs include several small mammal species, but birds may play an underrecognized role in human risk given their ability to disperse infected ticks across large spatial scales. Here, we provide a global synthesis of the ecological and evolutionary factors that determine the ability of bird species to infect larval ticks with Bbsl. LocationGlobal Time period1983 to 2019 Major taxa studiedBirds MethodsWe compiled a dataset of Bbsl competence across 183 bird species and applied meta-analysis, phylogenetic factorization, and boosted regression trees to describe spatial and temporal patterns in competence, characterize its phylogenetic distribution across birds, reconstruct its evolution, and evaluate the trait profiles associated with competent avian species. ResultsHalf of sampled bird species show evidence of competence for Bbsl. Competence displays moderate phylogenetic signal, has evolved multiple times across bird species, and is pronounced in the genus Turdus. Trait-based analyses distinguished competent birds with 80% accuracy and show that such species have low baseline corticosterone, exist on both ends of the pace-of-life continuum, breed and winter at high latitudes, and have broad migratory movements into their breeding range. We use these trait profiles to predict various likely but unsampled competent species, including novel concentrations of avian reservoirs within the Neotropics. Main conclusionOur results can generate new hypotheses for how birds contribute to the dynamics of tick-borne pathogens and help prioritize surveillance of likely but unsampled competent birds. Our findings further emphasize that birds display underrecognized variation in their contributions to enzootic cycles of Bbsl and the broader need to better consider competence in ecological and predictive studies of multi-host pathogens.

ecology↗

Temporal and spatial limitations in global surveillance for bat filoviruses and henipaviruses

Sampling reservoir hosts over time and space is critical to detect epizootics, predict spillover, and design interventions. However, because sampling is logistically difficult and expensive, researchers rarely perform spatiotemporal sampling of many reservoir hosts. Bats are reservoirs of many virulent zoonotic pathogens such as filoviruses and henipaviruses, yet the highly mobile nature of these animals has limited optimal sampling of bat populations. To quantify the frequency of temporal sampling and to characterize the geographic scope of bat virus research, we here collated data on filovirus and henipavirus prevalence and seroprevalence in wild bats. We used a phylogenetically controlled meta-analysis to next assess temporal and spatial variation in bat virus detection estimates. Our analysis shows that only one in four bat virus studies report data longitudinally, that sampling efforts cluster geographically (e.g., filovirus data are available across much of Africa and Asia but are absent from Latin America and Oceania), and that sampling designs and reporting practices may affect some viral detection estimates (e.g., filovirus seroprevalence). Within the limited number of longitudinal bat virus studies, we observed high heterogeneity in viral detection estimates that in turn reflected both spatial and temporal variation. This suggests that spatiotemporal sampling designs are essential to understand how zoonotic viruses are maintained and spread within and across wild bat populations, which in turn could help predict and preempt risks of zoonotic viral spillover.

epidemiology↗

Percolation models of pathogen spillover

A series of logical events must occur for a pathogen to spill over from animals to people. The pathogen must be present in an animal reservoir, it must be shed from the reservoir into the environment or be transferred from the reservoir to a vector, it must persist in the environment or vector until contact with a human or amplifier host, and it must successfully enter, colonize, and reproduce within the human. These events each represent a barrier the pathogen must cross to successfully infect a human. Percolation models of pathogens completing the series of barriers or logical events can connect models of spillover risk with standard tools for statistical inference.\n\nHere, we develop percolation-based models of spillover risk and a theoretical framework for managing spillover as an inextricably multilevel process. Through analysis and simulation, we show that estimated associations between level-specific covariates and spillover events will err towards associations from dominant pathway to spillover, a potential problem if there are alternative pathways to spillover with different associations with covariates. Furthermore, estimated associations between covariates and spillover will better reflect associations between covariates and success probabilities of bottleneck events with the highest pathogen attrition rates in the data observed. If one agrees with a percolation model for spillover, then GLMs should not be used to estimate relative importance of various levels. We recommend always using nonlinear models for predicting spillover risk with quantitative covariates and discuss why switching regression models may be well suited for avoiding some obvious pitfalls in predicting spillover from alternative pathways or wildlife reservoirs. Finally, we demonstrate how percolation models formalize an intuitive management paradigm for mitigating risk in the inherently multilevel process of pathogen spillover.

epidemiology↗

The fine-scale landscape of immunity and parasitism in a wild ungulate population

Spatial heterogeneity in parasite susceptibility and exposure is a common source of confounding variation in disease ecology studies. However, it is not known whether spatial autocorrelation acts on immunity in particular at small scales, within wild animal populations, and whether this predicts spatial patterns in infection. Here we used a well-mixed wild population of individually recognised red deer (Cervus elaphus) inhabiting a heterogeneous landscape to investigate fine-scale spatial patterns of immunity and parasitism. We noninvasively collected 842 faecal samples from 141 females with known ranging behaviour over two years. We quantified total and helminth-specific mucosal antibodies and counted propagules of three gastrointestinal helminth taxa. These data were analysed with linear mixed models using the Integrated Nested Laplace Approximation (INLA), using a Stochastic Partial Differentiation Equation approach (SPDE) to control for and quantify spatial autocorrelation. We also investigated whether spatial patterns of immunity and parasitism changed seasonally. We discovered substantial spatial heterogeneity in general and helminth-specific antibody levels and parasitism with two helminth taxa, all of which exhibited contrasting seasonal variation in their spatial patterns. Notably, strongyle nematode intensity did not align with density hotspots, while Fasciola hepatica intensity appeared to be strongly influenced by the presence of wet grazing. In addition, antibody hotspots did not correlate with distributions of any parasites. Our results suggest spatial heterogeneity may be an important factor affecting immunity and parasitism in a wide range of study systems. We discuss these findings with regards to the design of sampling regimes and public health interventions, and suggest that disease ecology studies investigate spatial heterogeneity more regularly to enhance their results, even when examining small geographic areas.

ecology↗

Phylogenetic factorization of mammalian viruses complements trait-based analyses and guides surveillance efforts

Predicting which novel microorganisms may spill over from animals to humans has become a major priority in infectious disease biology. However, there are few tools to help assess the zoonotic potential of the enormous number of potential pathogens, the majority of which are undiscovered or unclassified and may be unlikely to infect or cause disease in humans. We adapt a new biological machine learning technique - phylofactorization - to partition viruses into clades based on their non-human host range and whether or not there exist evidence they have infected humans. Our cladistic analyses identify clades of viruses with common within-clade patterns - unusually high or low propensity for spillover. Phylofactorization by spillover yields many clades of viruses containing few to no representatives that have spilled over to humans, including the families Papillomaviridae and Herpesviridae, and the genus Parvovirus. Removal of these non-zoonotic clades from previous trait-based analyses changed the relative significance of traits determining spillover due to strong associations of traits with non-zoonotic clades. Phylofactorization by host breadth yielded clades with unusually high host breadth, including the family Togaviridae. We identify putative life-history traits differentiating clades host breadth and propensities for zoonosis, and discuss how these results can prioritize sequencing-based surveillance of emerging infectious diseases.

epidemiology↗