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Streicker, D. G.

Publications and source records attributed to Streicker, D. G..

15 recordsLinked to original sources

Cross-Continental Analysis of Vampire Bat Betaherpesvirus Reveals Limited Interference Among Strains and Local Geographic Spread

Desmodus rotundus Betaherpesvirus (DrBHV) is a candidate vector for a transmissible vaccine targeting the circulation of rabies virus within its vampire bat reservoir. Studies assessing the potential for DrBHV as a vector have not considered its geographic range, potential for transboundary spread or how the diversity of wildtype DrBHV in natural bat populations might impede the spread of a modified vaccine strain. Here, by sequencing DrBHVs from vampire bats spanning 15 regions across 7 rabies-affected countries in Latin America and the Caribbean, we characterise the continent-scale distribution of DrBHV diversity and demonstrate widespread and apparently unconstrained co-infection. DrBHV occurred in all regions, forming a monophyletic clade consistent with a single introduction to vampire bats or host-virus co-speciation rather than frequent host switching. Phylogeographic analyses revealed cross-boundary spread that was predicted by geographic proximity. We identified 50 putative DrBHV strains and 79% of DrBHV-infected bats harboured multiple strains. No strains were over- or under-represented in co-infection and co-infections occurred proportionately to local strain prevalence. Whether strains circulated in given populations was predominantly driven by the geographic proximity of other populations containing that strain. The evolutionary relatedness of strains constrained neither rates of co-infection within individuals nor whether strains co-circulated within regions, suggesting vaccine vectors might be locally sourced rather than requiring imported, divergent strains to ameliorate interference. These results support the viability of DrBHV-vectored vaccines for mitigating rabies virus across Latin America and the Caribbean, despite widespread circulation of wildtype viruses.

genomics↗

Spillover of H5 influenza viruses to vampire bats at the marine-terrestrial interface

The highly pathogenic H5N1 avian influenza A virus (IAV) clade 2.3.4.4b has spread globally and spilled over into multiple mammalian species, raising concerns about its pandemic potential. In late 2022, clade 2.3.4.4b viruses devastated seabird and marine mammal populations along the Pacific coast of South America. Here, we report the first evidence of H5 IAV infections in wild bats globally, focusing on common vampire bats (Desmodus rotundus) in coastal areas of Peru. Longitudinal serological screening, stable isotope analysis and metabarcoding revealed repeated exposures to H5 IAVs in vampire bats which feed on coastal wildlife species heavily impacted by the 2.3.4.4b epizootic, but no evidence of infection in populations without access to marine prey. We further report bat gene flow between IAV-exposed and IAV-naive populations, and IAV infections in a vampire bat colony that fed on both marine and terrestrial livestock prey, providing insights into how future IAV epizootics might spread spatially within bats and between marine and terrestrial ecosystems if a bat reservoir were established. Immunohistochemistry demonstrated that the H5 haemagglutinin protein binds to the upper respiratory tract of vampire bats, suggesting bat tissue susceptibility to H5 IAVs. Finally, vampire bat-derived kidney, liver, and lung cells supported entry, replication, and egress of avian and mammalian 2.3.4.4b viruses, confirming cellular infectivity. These results illustrate how combining ecological inference and experimental virology can pinpoint the species origins and biological significance of viral spillover at species interfaces. Recurrent exposures from marine wildlife, tissue and cellular susceptibility to H5N1 IAVs, and connections to other IAV-susceptible terrestrial mammals establish the prerequisite conditions for vampire bats to spread IAVs between marine and terrestrial environments or to form a novel reservoir of highly pathogenic IAVs.

ecology↗

Mating behaviour and connectivity drive sporadic European bat lyssavirus 2 infections in Myotis myotis

Gaining insight into the transmission and persistence of zoonoses in wild reservoirs is essential for preventing outbreaks, assessing demographic impacts, and informing conservation strategies. Achieving this requires reliable estimates of key epidemiological parameters, which are governed by aspects of host ecology and behaviour that are notoriously difficult to quantify in many wild species. Taking advantage of a long term study of the ecology of five Greater mouse-eared bats (Myotis myotis) maternity colonies in France ([~]2700 marked individuals), we sought to characterise lyssavirus infection dynamics in a wild bat reservoir. Although no lyssavirus was isolated from any of the 422 saliva samples tested, we report the first indirect evidence of European bat lyssavirus 2 circulation in this species. Interestingly, seropositivity appeared sporadic within colonies (0-100% annually) and synchronized across them, with highest seroprevalence in 2015-2017, but remaining low otherwise. Fitting Bayesian compartmental epidemiological models, we found that shifts in EBLV-2 prevalence were primarily driven by mating season introduction, age-dependant variation in transmission, and frequency-dependent transmission dynamics. Lyssavirus outbreaks involve few deaths overall but can still yield high annual mortality rates. These findings underscore the value of integrating ecological and individual-level data with mechanistic modelling to enhance our understanding and management of zoonotic pathogens in wildlife.

ecology↗

Experimental infections reveal unexceptional viral tolerance in bats

A common explanation for bats being a conspicuous source of zoonotic viruses is their purported ability to coexist with viruses without suffering overt disease. This belief has catalyzed the discovery of unique features of bat immune systems which may have translational value as broad-spectrum antivirals, particularly if they evolved as a byproduct of bats' unique life history rather than through conventional co-evolutionary processes. Surprisingly, whether bats compared to other host groups suffer less disease from co-evolved viruses or from viruses generally has not been formally assessed. Here, synthesizing eighty-six years of experimental infections, involving 54 viruses, 85 host species, and over 5,600 animals, we document disease in bats following inoculation by taxonomically diverse viruses, including ones that are relatively benign in humans. The occurrence of overt disease, the likelihood of mortality, and the severity of disease in bats were indistinguishable from those experienced by rodents, another group associated with many zoonotic viruses. These patterns were consistent when considering only bat-associated viruses inoculated into bats and rodent-associated viruses inoculated into rodents and among inoculations which lacked shared co-evolutionary history. Instead, disease outcomes following infection were shaped by experimental design, viral host range, and evolutionary context. Unexceptional disease in bats from novel or co-evolved infections suggests that order-level host life history traits such as flight have inconsistent consequences for antiviral immunity and highlights the need to evaluate the functional properties of putatively unique features of bat immunity in vivo. These results do not exclude the possibility of developing broader-acting or more potent antivirals from bat immune systems nor do they diminish the potential value of mechanistic insights into bat immunity. However, they do not support the premise underlying the idea that bats will be an unusually rich source of future biomedical breakthroughs.

evolutionary biology↗

An optimized rabies vaccine vehicle for orotopical administration to wild vampire bats.

Rabies vaccination of vampire bats (Desmodus rotundus) has been proposed as a superior control method to culling but has yet to be implemented. Success of rabies vaccination depends on a topical vehicle that spreads through a bat colony via allogrooming while additionally preserving vaccine immunogenicity. This work describes the in vitro and in vivo optimization of a new orotopical gel for rabies vaccine delivery to vampire bats. Autonomous transferability of our carboxymethyl cellulose (CMC) gel vaccine delivery formulation was tested in a microchipped vampire bat colony in rural Jalisco, Mexico. Intra-colony gel uptake was traced using the fluorescent biomarker rhodamine B. Importantly, application of topical treatment of [~]20% of the bat colony resulted in estimated uptake by over 85% of the colony. The in vitro stability of our raccoon poxviral-vectored rabies vaccine candidate within CMC was measured at time points up to 3 months at 40 {degrees}C, 23 {degrees}C, and 4 {degrees}C. Extended storage at 4 {degrees}C and short exposure at higher temperatures of potential vampire bat environments preserved vaccine titers within CMC. Furthermore, physical properties of our CMC formulation were compared to the previously used glycerin jelly at 40 {degrees}C, 20 {degrees}C, and 0 {degrees}C using rheological tests. These tests indicate that CMC exhibits optimal properties for topical application to bats even at extreme temperatures possible during field vaccination. This study advances our rabies vaccination strategy for vampire bats by providing a topical vehicle suitable for field application that may additionally be employed for other significant bat diseases.

ecology↗

Diverse behavioural responses of vampire bats to human disturbance revealed by state-space modelling of sparse GPS data.

In Latin America, management of vampire bats has had inconsistent effects on the spread of lethal rabies infections from bats to humans and livestock. Positive and negative effects on rabies are hypothesised to reflect changes in bat roost fidelity and behaviour following human disturbance, but high landscape complexity has precluded monitoring bat movement in the areas where rabies transmission and bat management activity are most intense. We used animal-borne GPS tags to track 93 vampire bats in a rabies hotspot in the Peruvian Andes, where limited satellite visibility led to partial observation of animal locations. Immediately after capture, handling and tag application, 43% of bats, particularly males and bats with longer forearms, disappeared from the study area, suggesting a rapid roost switching response. Among the remaining 55 bats, a Bayesian state-space model revealed high individual heterogeneity on the disturbance night but on average increased flight distances. Over the remaining 8-night study period, bats gradually remained closer to the roost. These disturbance-driven shifts provide mechanisms to explain how bat disturbance can both accelerate and decelerate rabies spatial spread. More broadly, we present a modelling framework to infer key movement metrics in landscapes where GPS data limitations challenge conventional movement models.

ecology↗

Dynamics of influenza transmission in vampire bats revealed by longitudinal monitoring and a large-scale anthropogenic perturbation

Interrupting pathogen transmission between species is a priority strategy to mitigate zoonotic threats. However, avoiding counterproductive interventions requires knowing animal reservoirs of infection and the dynamics of transmission within them, neither of which are easily ascertained from the cross-sectional surveys which currently dominate investigations into newly discovered viruses. We used biobanked sera and metagenomic data to reconstruct the transmission of recently discovered bat-associated influenza virus (BIV) over 12 years in three zones of Peru. Mechanistic models fit under a Bayesian framework, which enabled joint inference from serological and molecular data, showed that common vampire bats maintain BIV independently of the currently assumed fruit bat reservoir through immune waning and seasonal transmission pulses. A large-scale vampire bat cull targeting rabies incidentally halved BIV transmission, confirming vampire bats as maintenance hosts. Our results show how combining field studies, perturbation responses and multi-data type models can elucidate pathogen dynamics in nature and reveal pathogen-dependent effects of interventions.

ecology↗

Population genetics, phylogeography and gene flow of mainland and island vampire bat (Desmodus rotundus) populations: an investigation into mainland-island bat movement

Movement of animals and plants from mainland populations contributes to the genetic diversity and viability of geographically isolated island biota, but also carries risks of pathogen introductions. The bat fauna of the island of Trinidad reflects species diversity on the neighbouring South American mainland and includes the common vampire bat (Desmodus rotundus). We determined relationships between Trinidad and mainland vampire bat populations and the extent of mainland-island movement by comparing the genetic structure (nuclear and mitochondrial) and morphology of the Trinidadian D. rotundus population to populations in neighbouring regions of the South American mainland and estimating evolutionary histories and patterns of gene flow. Results indicate that Trinidadian D. rotundus are genetically and morphologically distinct from mainland populations, although limited unidirectional male-biased mainland to island gene flow occurs at an estimated rate of 3.3 migrants per year. Two geographically-defined Desmodus cytochrome b clades were identified within Trinidad (i.e., one restricted to the South-Western peninsula which grouped with Venezuelan sequences and the other found throughout the rest of the island which grouped with sequences from Suriname and Guyana) suggesting long-standing female philopatry. The geographic distribution of these clades mirrors that of two previously identified geographically defined rabies virus (RABV) lineages introduced to Trinidad from the mainland. This finding suggests that bat dispersals and RABV introductions occur via both the northern and south-western island peninsulas, with subsequent male-driven intra-island viral spread enabled by bat nuclear homogeneity of these populations. These study findings will contribute to the development of contemporary evidence-based vampire bat population control and rabies prevention programs within island populations.

evolutionary biology↗

Incorporating environmental heterogeneity and observation effort to predict host distribution and viral spillover from a bat reservoir.

Predicting the spatial occurrence of wildlife is a major challenge for ecology and management. In Latin America, knowledge of the true number and locations of vampire bat colonies precludes informed allocation of measures intended to limit lethal rabies spillover to humans and livestock. We inferred the complete spatial distribution of vampire bat roosts while accounting for observation effort and environmental covariates by fitting a Log Gaussian Cox Process model to the locations of 563 roosts in three regions of Peru. Our model explained 47% of the variance in the observed roost distribution and identified landscape correlates of roost establishment. Our model estimated that 1,795 roosts (76%) remain undiscovered and identified hotspots of undetected roosts in currently rabies-free areas, implying high risk for viral incursion. Incorporating the locations of undetected roosts improved spatial predictions of rabies spillover to livestock, revealed areas with disproportionate underreporting to surveillance systems, and indicated a higher rabies burden than previously estimated. We provide a robust approach to infer the distribution of a mostly unobserved bat reservoir that can inform strategies to prevent the re-emergence of an important zoonosis.

ecology↗

Variation in the ACE2 receptor has limited utility for SARS-CoV-2 host prediction

Transmission of SARS-CoV-2 from humans to other species threatens wildlife conservation and may create novel sources of viral diversity for future zoonotic transmission. A variety of computational heuristics have been developed to pre-emptively identify susceptible host species based on variation in the ACE2 receptor used for viral entry. However, the predictive performance of these heuristics remains unknown. Using a newly-compiled database of 96 species we show that, while variation in ACE2 can be used by machine learning models to accurately predict animal susceptibility to sarbecoviruses (accuracy = 80.2%, binomial confidence interval [CI]: 70.8 - 87.6%), the sites informing predictions have no known involvement in virus binding and instead recapitulate host phylogeny. Models trained on host phylogeny alone performed equally well (accuracy = 84.4%, CI: 75.5 - 91.0%) and at a level equivalent to retrospective assessments of accuracy for previously published models. These results suggest that the predictive power of ACE2-based models derives from strong correlations with host phylogeny rather than processes which can be mechanistically linked to infection biology. Further, biased availability of ACE2 sequences misleads projections of the number and geographic distribution of at-risk species. Models based on host phylogeny reduce this bias, but identify a very large number of susceptible species, implying that model predictions must be combined with local knowledge of exposure risk to practically guide surveillance. Identifying barriers to viral infection or onward transmission beyond receptor binding and incorporating data which are independent of host phylogeny will be necessary to manage the ongoing risk of establishment of novel animal reservoirs of SARS-CoV-2.

microbiology↗

A two-step metagenomics approach for prey identification from the blood meals of common vampire bats (Desmodus rotundus)

The feeding behaviour of the sanguivorous common vampire bat (Desmodus rotundus) facilitates the transmission of pathogens that can impact both human and animal health. To formulate effective strategies in controlling the spread of diseases, there is a need to obtain information on which animals they feed on. One DNA-based approach, shotgun sequencing, can be used to obtain such information. Even though it is costly, shotgun sequencing can be used to simultaneously retrieve prey and vampire bat mitochondrial DNA for population studies within one round of sequencing. However, due to the challenges of analysing shotgun sequenced metagenomic data such as false negatives/positives and typically low proportion of reads mapped to diet items, shotgun sequencing has not been used for the identification of prey from common vampire bat blood meals. To overcome these challenges and generate longer mitochondrial contigs which could be useful for prey population studies, we shotgun sequenced common vampire bat blood meal samples (n=8) and utilised a two-step metagenomic approach based on combining existing bioinformatic workflows (alignment and de novo mtDNA assembly) to identify prey. Further, we validated our results to detections made through metabarcoding. We accurately identified the common vampire bats prey in seven out of eight samples without any false positives. We also generated prey mitochondrial contig lengths between 138bp to 3231bp (mean=985bp, SD=981bp). As we develop more computationally efficient bioinformatics pipelines and reduce sequencing costs, we can expect an uptake in metagenomics dietary studies in the near future.

molecular biology↗

Respiratory disease in cats associated with human-to-cat transmission of SARS-CoV-2 in the UK

Two cats from different COVID-19-infected households in the UK were found to be infected with SARS-CoV-2 from humans, demonstrated by immunofluorescence, in situ hybridisation, reverse transcriptase quantitative PCR and viral genome sequencing. Lung tissue collected post-mortem from cat 1 displayed pathological and histological findings consistent with viral pneumonia and tested positive for SARS-CoV-2 antigens and RNA. SARS-CoV-2 RNA was detected in an oropharyngeal swab collected from cat 2 that presented with rhinitis and conjunctivitis. High throughput sequencing of the virus from cat 2 revealed that the feline viral genome contained five single nucleotide polymorphisms (SNPs) compared to the nearest UK human SARS-CoV-2 sequence. An analysis of cat 2s viral genome together with nine other feline-derived SARS-CoV-2 sequences from around the world revealed no shared catspecific mutations. These findings indicate that human-to-cat transmission of SARS-CoV-2 occurred during the COVID-19 pandemic in the UK, with the infected cats developing mild or severe respiratory disease. Given the versatility of the new coronavirus, it will be important to monitor for human-to-cat, cat-to-cat and cat-to-human transmission.

microbiology↗

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↗

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↗

Dynamics of viral index infections in novel hosts

Whether a pathogen entering a new host species results in a single infection or in onward transmission, and potentially an outbreak, depends upon the progression of infection in the index case. Although index infections are rarely observable in nature, experimental inoculations of pathogens into novel host species have a long history in biomedical research. This provides a rich and largely unexploited data source for meta-analyses to identify the host and pathogen determinants of variability in infection outcomes. Here, we analysed the progressions of 514 experimental cross-species inoculations of rabies virus, a widespread zoonotic pathogen which in nature exhibits both dead end infections and varying levels of sustained transmission in novel hosts. Inoculations originating from bats rather than carnivores, and from warmer to cooler-bodied species caused infections with shorter incubation periods that were associated with diminished virus excretion. Inoculations between distantly related hosts tended to result in shorter clinical disease periods, which will also impede transmission. All effects were modulated by infection dose and together suggest that increased virulence as host species become more dissimilar is the limiting factor preventing onward transmission. These results explain observed constraints on rabies virus host shifts, allow us to evaluate the risk of novel reservoirs establishing, and give mechanistic insights into why host shifts are less likely between genetically distant species. More generally, our study highlights meta-analyses of experimental infections as a tractable approach to quantify the complex interactions between virus, reservoir, and novel host that shape the outcome of cross-species transmission. Significance statementEmerging disease epidemics often result from a pathogen establishing transmission in a novel host species. However, most cross-species transmissions fail to establish in the newly infected species for reasons that remain poorly understood. Examining cross-species inoculations involving rabies, a widespread viral zoonosis, we show that mismatches in virulence, which are predictable from host and viral factors, make sustained transmission in the novel host less likely. In particular, disease progression was accelerated and virus excretion decreased when the reservoir and novel host were physiologically or genetically more dissimilar. These mechanistic insights help to explain and predict host shift events and highlight meta-analyses of existing experimental inoculation data as a powerful and generalisable approach for understanding the dynamics of index infections in novel species.

ecology↗