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Gubbins, S.

Publications and source records attributed to Gubbins, S..

16 recordsLinked to original sources

Evolutionary analysis supports variation in life history strategies between three foot-and-mouth-disease-virus serotypes

Viruses have diverse life history strategies driven by variation in traits such as infectivity, transmission mode, and length and severity of infection that affect their epidemiology and evolution. While well documented among different species, life history and phenotypic variation among variants of the same virus species are less well understood. Foot-and-mouth-disease-virus (FMDV) is an ungulate-infecting picornavirus endemic to many regions, including Sub-Saharan Africa, where it circulates between wildlife and livestock in several serotypes. Recent work suggested that FMDV variants from the three Southern-African Territories serotypes exhibit different life history strategies, with these dynamics potentially causing distinct signatures in viral evolutionary rate, transmission among host species, and movement among regions. To investigate whether any effects of predicted effects occurred in natural settings, and whether these differences were shared with other strains within each serotype, this study used 716 published FMDV sequences (approximately 430bp) from 3 serotypes (SAT1, SAT2, and SAT3) to measure and compare evolutionary rates and transmission between regions and host types in Southern Africa. SAT1 had a slower rate of evolution consistent with a predicted more chronic infection strategy, and SAT2 had higher variability in evolutionary rates and some evidence of transmission from livestock to wildlife, suggesting livestock may play a part in persistence. SAT3 showed an expected intermediate phenotype but was challenging to validate due to small sample size. All SATs showed similar levels of transmission between regions. These results suggest that SAT1, SAT2, and SAT3 exhibit different transmission dynamics and evolutionary signatures, consistent with different life history strategies observed in their representative strains, such as more latency or a multi-host maintenance community.

evolutionary biology↗

Defining the transmission parameters of lumpy skin disease virus by the three model insect vector species Aedes aegypti, Stomoxys calcitrans and Culicoides nubeculosus reveals important differences in their likely role in transmission

Lumpy skin disease virus (LSDV) is a poxvirus that can cause severe, systemic disease in cattle. By far the most important route of transmission of LSDV is mechanical transmission via haematophagous arthropod vectors. However we lack detailed information on this process including the likelihood of transmission by different vector species. This study used an experimental bovine model of LSDV transmission to quantify the transmission of LSDV from an infected donor to a naive recipient calf. Three species of Diptera representing different vector groups were included (Stomoxys calcitrans, Aedes aegypti and Culicoides nubeculosus, respectively a large biting fly, a mosquito and a midge), and the clinical, virological and immunological outcomes in the recipient calves studied. The ability of Ae. aegypti to mechanically transmit LSDV following feeding on an artificial membrane feeding system was also examined. Both Ae. aegypti and S. calcitrans were able to transmit LSDV, resulting in disease in recipient calves. Bites from virus-positive C. nubeculosus did not result in disease in recipient calves, though the presence of neutralising antibodies in these recipients indicated exposure to virus or virus components. Ae. aegypti successfully transmitted LSDV following feeding on LSDV-spiked blood through an artificial membrane feeding system, validating this laboratory model as a future replacement for donor cattle. Mathematical models of the data were generated and predicted S. calcitrans to be the most efficient vector of LSDV of the insects tested with a reproduction number (R0) of 5.8. Impact statementLumpy skin disease virus (LSDV) is a neglected, rapidly emerging pathogen of cattle that has spread into Europe and throughout the Middle East and Asia over the past ten years. Lack of understanding of the mechanism of transmission of LSDV has hampered efforts to control its rapid spread. This study compares the ability of three model species of Diptera (Stomoxys calcitrans, Aedes aegypti and Culicoides nubeculosus) to mechanically transmit the virus to cattle, generating high quality quantitative data to facilitate mathematical modelling of virus transmission. S. calcitrans was identified as a potential driver of LSDV transmission with a R0 of 5.8. This work provides new insights into the vector transmission of LSDV that can be used to design more targeted and effective disease control programmes.

microbiology↗

Pathogenesis and immune response to respiratory coronaviruses in their natural porcine host

Porcine respiratory coronavirus (PRCV) is a naturally occurring pneumotropic coronavirus in the pig, providing a valuable large animal model to study acute respiratory disease. PRCV pathogenesis and the resulting immune response was investigated in pigs, the natural large animal host. We compared two strains, ISU-1 and 135, which induced differing levels of pathology in the respiratory tract to elucidate the mechanisms leading to mild or severe disease. The 135 strain induced greater pathology which was associated with higher viral load and stronger spike-specific antibody and T cell responses. In contrast, the ISU-1 strain triggered mild pathology with a more balanced immune response and greater abundance of T regulatory cells. A higher frequency of putative T follicular helper cells was observed in animals infected with strain 135 at 11 days post-infection. Single-cell RNA-sequencing of bronchoalveolar lavage revealed differential gene expression in B and T cells between animals infected with 135 and ISU-1 at 1 day post infection. These genes were associated with cell adhesion, migration, and immune regulation. Along with increased IL-6 and IL-12 production, these data suggest that heightened inflammatory responses to the 135 strain may contribute to pronounced pneumonia. Among BAL immune cell populations, B cells and plasma cells exhibited the most gene expression divergence between pigs infected with different PRCV strains, highlighting their potential role in maintaining immune homeostasis in the respiratory tract. These findings indicate the potential of the PRCV model for studying coronavirus induced respiratory disease and identifying mechanisms that determine infection outcomes. Author summaryUnderstanding how our immune system reacts to respiratory viruses, like SARS-CoV-2, is crucial to developing better treatments. While most COVID-19 infections are mild, some cases lead to severe lung damage, but we do not fully understand why. To study this, we used pigs, which respond more like humans compared to small animals, to explore how the immune system deals with respiratory coronaviruses. We tested two porcine respiratory coronavirus strains that caused different levels of lung damage. The more severe strain triggered a strong immune response and high inflammation, leading to lung pathology similar to that seen in severe COVID-19 cases. By contrast, the milder strain caused a balanced immune response, including more regulatory T cells that help control inflammation. We also found changes in genes related to antibody-producing cells, which may be important for controlling respiratory pathology. Interestingly, changes in immune responses and gene expression lasted long after the virus was cleared, potentially making individuals more vulnerable to future infections - similar to the "long COVID" symptoms seen in people. We propose that this pig model could help us study coronavirus-induced lung damage and test new therapies to prevent severe disease.

immunology↗

Using the basic reproduction ratio to quantify transmission and identify data gaps for epizootic haemorrhagic disease, an emerging vector-borne disease in Europe

Epizootic haemorrhagic disease virus (EHDV) is an arbovirus transmitted by Culicoides biting midges that has recently emerged in Europe. Here, the basic reproduction ratio (R0) was used to quantify the transmission of EHDV and its dependence on temperature for cattle and deer. Using data from the published literature the parameters needed to calculate R0 were estimated with Bayesian methods to incorporate uncertainty in the calculations. The Sobol method of sensitivity analysis was used to determine the parameters having the greatest influence on R0 and, hence, to identify important data gaps. Depending on the strain the maximum R0 for EHDV varied from 0.7 to 2.5 in cattle and 1.3 to 4.3 in deer. The maximum R0 occurred at temperatures between 22 and 25 {degrees}C, while the lowest temperature at which R0 exceeded one was between 16 and 20 {degrees}C. The sensitivity analysis identified the threshold temperature for virus replication, the probability of transmission from host to vector and the vector to host ratio as the most important parameters influencing R0. Furthermore, there are only limited data on EHDV in European deer species and on transmission in wildlife and at the livestock/wildlife interface. These data gaps should be the focus of future research.

microbiology↗

Quantifying the relationship between within-host dynamics and transmission for viral diseases of livestock

Understanding the population dynamics of an infectious disease requires linking within-host dynamics and between-host transmission in a quantitative manner, but this is seldom done in practice. Here a simple phenomenological model for viral dynamics within a host is linked to between-host transmission by assuming that the probability of transmission is related to log viral titre. Data from transmission experiments for two viral diseases of livestock, foot-and- mouth disease virus in cattle and swine influenza virus in pigs, are used to parameterise the model and, importantly, test the underlying assumptions. The model allows the relationship between within-host parameters and transmission to be determined explicitly through their influence on the individual reproduction number and generation time. Furthermore, these critical within-host parameters (time and level of peak titre, viral growth and clearance rates) can be computed from more complex within-host models, raising the possibility of assessing the impact of within-host processes on between-host transmission in a more detailed quantitative manner. Author summaryFor a pathogen to be able to transmit between hosts it must replicate to a sufficiently high level within an infected host. Because of this linking the dynamics of a pathogen within a host to transmission between hosts is important for understanding an infectious disease and its control. In this study I develop a simple mathematical model for the within-host dynamics and combine it with a model relating the probability of transmission to the level of the pathogen. I use the model derive explicit relationships between parameters related to the within-host dynamics, such as viral growth and clearance rates, and summary transmission measures, such as the reproduction number and generation time. I test the assumptions in the underlying model and estimate parameters using data from transmission experiments for two important viral diseases, foot-and-mouth disease virus in cattle and swine influenza virus in pigs. Identifying the critical within host parameters that influence transmission allows the impact of within-host processes on between-host transmission to be investigated in a more detailed quantitative manner.

microbiology↗

The mechanical arthropod vector Stomoxys calcitrans influences the outcome of lumpy skin disease virus infection in cattle

The poxvirus lumpy skin disease virus (LSDV) is the etiological agent of lumpy skin disease (LSD), a severe disease of cattle and water buffalo that is characterised by numerous necrotic cutaneous nodules. LSD is a rapidly emerging disease, spreading into and across the Middle East, eastern Europe, and Asia in the past decade. The disease causes substantial production and economic losses in rural communities and affected regions. LSDV is mechanically transmitted by haematophagous arthropods including stable flies (Stomoxys calcitrans), however our understanding of this mechanical transmission method is sparse. A secreted saliva collection methodology using a modified artificial membrane feeding system was optimised for S. calcitrans and used to collect and characterise secreted S. calcitrans saliva. Saliva was mixed with LSDV and shown not to affect virus growth in primary bovine fibroblasts. S. calcitrans saliva or spot-feeding by S. calcitrans was then incorporated into a bovine in vivo experimental model of LSD to determine if either influenced disease pathogenesis. S. calcitrans saliva resulted in fewer animals developing disease, however this difference was not statistically significant. Spot-feeding with S. calcitrans prior to inoculation did not alter the number of animals that developed disease or the overall severity of disease however disease progression was accelerated as demonstrated by the appearance of cutaneous nodules, detection of viral DNA in the blood stream, and production of neutralising antibodies. This shows that S. calcitrans influence disease kinetics through co-incident bite trauma and/or saliva deposition. This increases our understanding of LSDV pathogenesis and highlights the overlooked importance of mechanical vectors in pathogen transmission. Author summaryInsect vectors are important conduits for the transmission of pathogens that cause diseases such as Zika, dengue, malaria, and lumpy skin disease. Biological vector-borne transmission incorporates a replication phase for the pathogen in the insect, whereas no replication occurs in the vector during mechanical transmission. When the insect bites the host it inoculates a pathogen whilst also delivering arthropod-derived factors such as saliva components and causing tissue trauma through biting and probing. Arthropod saliva and/or bite trauma have been shown to enhance the speed and severity of disease following inoculation with a range of biologically transmitted viruses. This study examined if this was true also for the mechanically transmitted pathogen lumpy skin disease virus (LSDV). LSDV is a neglected pathogen that causes severe systemic disease in cattle and is transmitted mechanically by the stable fly Stomoxys calcitrans. Using an experimental bovine model of LSD, we found that disease occurred more rapidly when virus was delivered in association with the bites of uninfected flies. This work has increased our knowledge of lumpy skin disease virus transmission, and the discovery that disease outcome can be impacted by previously overlooked mechanical insect vectors should prompt further investigation into this mechanism of transmission.

microbiology↗

Consilience in disease ecology: FMDV transmission dynamics reflect viral growth and immune response rates.

Infectious disease dynamics operate across biological scales: pathogens replicate within hosts but transmit among populations. Functional changes in the pathogen-host interaction thus generate cascading effects across organizational scales. We investigated within-host dynamics and among-host transmission of three strains (SAT-1, 2, 3) of foot-and-mouth disease viruses (FMDVs) in their wildlife host, African buffalo. We combined data on viral dynamics and host immune responses with mathematical models to ask (i) How do viral and immune dynamics vary among strains?; (ii) Which viral and immune parameters determine viral fitness within hosts?; and (iii) How do within-host dynamics relate to virus transmission? Our data reveal contrasting within-host dynamics among viral strains, with SAT-2 eliciting more rapid and effective immune responses than SAT-1 and SAT-3. Within-host viral fitness was overwhelmingly determined by variation among hosts in immune response activation rates but not by variation among individual hosts in viral growth rate. Our analyses investigating across-scale linkages indicate that viral replication rate in the host correlates with transmission rates among buffalo and that adaptive immune activation rate determines the infectious period. These parameters define the viruss relative basic reproductive number ([R]0), suggesting that viral invasion potential may be predictable from within-host dynamics.

ecology↗

Inferring transmission routes for foot-and-mouth disease virus within a cattle herd using approximate Bayesian computation

To control an outbreak of an infectious disease it is essential to understand the different routes of transmission and how they contribute to the overall spread of the pathogen. With this information, policy makers can choose the most efficient methods of detection and control during an outbreak. Here we demonstrate a method for assessing the contribution of different routes of transmission using approximate Bayesian computation with sequential Monte Carlo sampling (ABC-SMC). We apply this to infer parameters of an individual based model of within-herd transmission of foot-and-mouth disease virus (FMDV), incorporating transmission through direct contact and via environmental contamination. Additionally, we use ABC-SMC for model selection to assess the plausibility of either transmission route alone being responsible for all infections. We show that direct transmission likely contributes the majority of infections during an outbreak of FMD but there is an accumulation of environmental contamination that can cause infections within a farm and also have the potential to spread between farms via fomites.

zoology↗

Viral dynamics and immune responses to foot-and-mouth disease virus in African buffalo (Syncerus caffer).

Foot-and-mouth disease (FMD) is one of the most important livestock diseases restricting international trade. While it is clear that African buffalo (Syncerus caffer) act as the main wildlife reservoir, viral and immune response dynamics during FMD virus acute infection have not been described before in this species. We used experimental needle inoculation and contact infections with three Southern African Territories serotypes to assess clinical, virological and immunological dynamics for thirty days post infection. Clinical FMD in the needle inoculated buffaloes was mild and characterised by pyrexia. Despite the absence of generalised vesicles, all contact animals were readily infected with their respective serotypes within the first 2-9 days after being mixed with needle challenged buffaloes. Irrespective of the route of infection or serotype there were positive associations between the viral loads in blood and the induction of host innate pro-inflammatory cytokines and acute phase proteins. Viral loads in blood and tonsils were tightly correlated during the acute phase of the infection, however, viraemia significantly declined after a peak at 4 days post infection (dpi), which correlated with the presence of detectable neutralising antibodies. In contrast, infectious virus was isolated in the tonsils until the last sampling point (30 dpi) in most animals. The pattern of virus detection in serum and tonsil swabs was similar for all three serotypes in the direct challenged and contact challenged animals. We have demonstrated for the first time, that African buffalo are indeed systemically affected by FMD virus and clinical FMD in buffalo is characterized by a transient pyrexia. Despite the lack of FMD lesions, infection of African buffalo was characterised by high viral loads in blood and oropharynx, rapid and strong host innate and adaptive immune responses and high transmissibility.

zoology↗

Spatial, temporal and molecular dynamics of swine influenza virus-specific CD8 tissue resident memory T cells.

We defined naive, central memory, effector memory and terminally differentiated porcine CD8 T cells and analyzed their phenotype in lymphoid and respiratory tissues after influenza infection or immunization using peptide-MHC tetramers of three influenza nucleoprotein (NP) epitopes. The hierarchy of response to the three epitopes changes during the response in different tissues. Most NP-specific CD8 T cells in broncho-alveolar lavage (BAL) and lung are tissue resident memory cells (TRM), that express CD69 and have an effector memory or terminally differentiated phenotype. NP-specific cells isolated from BAL express genes characteristic of TRM, but gene expression differs at 7, 21 and 63 days post infection. The frequency of NP-specific cells declines over 63 days in all tissues but is best maintained in BAL. The pig is a powerful model for understanding how best to induce and harness local immunity to respiratory viruses. One sentence summaryInfluenza NP-specific porcine tissue resident memory CD8 T cells persist in the lung with major changes in gene expression.

immunology↗

Natural reassortment of a segmented RNA arbovirus illustrates plasticity of phenotype in the arthropod vector and mammalian host in vivo

Segmented RNA viruses are a taxonomically diverse group of 11 families that can infect plant, wildlife, livestock and human hosts. A shared feature of these viruses is the ability to exchange genome segments during co-infection of a host by a process termed reassortment. Reassortment enables rapid evolutionary change, but in the case of segmented RNA viruses utilising an arthropod vector is set against the constraint of purifying selection and genetic bottlenecks imposed by replication in two evolutionarily distant hosts. In this study, we use an in vivo host: arbovirus: vector model to investigate the impact of reassortment on two phenotypic traits: vector competence and virulence in the host. Bluetongue virus (BTV) (Reoviridae) is the causative agent of bluetongue (BT), an economically important disease of domestic and wild ruminants and deer. The genome of BTV is comprised of 10 linear segments of dsRNA and the virus is transmitted between ruminants by Culicoides biting midges (Diptera: Ceratopogonidae). Five strains of BTV representing three serotypes (BTV-1, BTV-4 and BTV-8) were isolated from naturally infected ruminants in Europe and parental/reassortant lineage status assigned through full genome sequencing. Each strain was then assessed in parallel for the ability to infect Culicoides and to cause BT in sheep. Our results demonstrate that two reassortment strains, which themselves became established in the field, had obtained high replication ability in C. sonorensis from one of the parental virus strains which allowed inferences of the genome segments conferring this phenotypic trait. IMPORTANCEReassortment between strains can lead to major shifts in the transmission parameters and virulence of segmented RNA viruses with consequences for spread, persistence and impact. The ability of these pathogens to change their phenotypes rapidly in response to selection pressure in new environments presents a major challenge in understanding factors driving emergence. Utilising a natural mammalian host-insect vector infection and transmission model, we demonstrated for the first time the genetic basis for a phenotypic trait of BTV within strains directly isolated from the field and, hence, selected and relevant for natural transmission.

microbiology↗

Inferring within-flock transmission dynamics of highly pathogenic avian influenza (H5N8) in France, 2020

Following the emergence of highly pathogenic avian influenza (H5N8) in France in early December 2020, we used duck mortality data of the index case to investigate within-flock transmission dynamics. A stochastic epidemic model was adjusted to the daily mortality data and model parameters were estimated using an approximate Bayesian computation sequential Monte Carlo (ABC-SMC) algorithm. Results suggested that the virus was introduced 4 days (95% credible interval: 3 - 5) prior to the day suspicion was reported and that the transmission rate was 3.7 day-1 (95%CI: 2.6 - 5.3). On average, ducks started being infectious 3.1 hours (95%CI: 0.4 - 8.0) after infection and remained infectious for 4.4 days (95%CI: 3.1 - 5.6). Model outputs also suggested that the number of infectious ducks was already 3239 (95%CI: 26 - 3706) the day before suspicion, emphasising the substantial latent threat this virus could pose to other poultry farms and to neighbouring wildlife. These estimations can be applied to upcoming outbreaks and made available to veterinary services within few hours. This study illustrates how mechanistic models can provide rapid relevant insights to contribute to the management of infectious disease outbreaks of farmed animals.

ecology↗

Magnitude and kinetics of T cell and antibody responses during H1N1pdm09 infection in outbred and inbred Babraham pigs

We have used the pig, a large natural host animal for influenza with many physiological similarities to humans, to characterize {beta}, {gamma}{delta} T cell and antibody (Ab) immune responses to the 2009 pandemic H1N1 virus infection. We evaluated the kinetic of virus infection and associated response in inbred Babraham pigs with identical MHC (Swine Leucocyte Antigen) and compared them to commercial outbred animals. High level of nasal virus shedding continued up to day 4-5 post infection followed by a steep decline and clearance of virus by day 9. Adaptive T cell and Ab responses were detectable from day 5-6 post infection reaching a peak at 9-14 days. {gamma}{delta} cells produced cytokines ex vivo at day 2 post infection, while virus specific IFN{gamma} producing {gamma}{delta} T cells were detected from day 7 post infection. Analysis of NP tetramer specific and virus specific CD8 and CD4 T cells in blood, lung, lung draining lymph nodes and broncho-alveolar lavage (BAL) showed clear differences in cytokine production between these tissues. BAL contained the most highly activated CD8, CD4 and {gamma}{delta} cells producing large amounts of cytokines, which likely contribute to elimination of virus. The weak response in blood did not reflect the powerful local lung immune responses. The immune response in the Babraham pig following H1N1pdm09 influenza infection was comparable to that of outbred animals. The ability to utilize these two swine models together will provide unparalleled power to analyse immune responses to influenza.

immunology↗

Quantifying the acquisition and retention of lumpy skin disease virus by haematophagus insects and the implications for transmission and control.

Lumpy skin disease virus (LSDV), a poxvirus that causes severe disease in cattle, has in the last few years rapidly extended its distribution from Africa and the Middle East into Europe, Russia, and across Asia. LSDV is believed to be primarily spread mechanically by blood-feeding arthropods, however the exact mode of arthropod transmission, the relative ability of different arthropod species to acquire and retain the virus, as well as their comparative importance for LSDV transmission, remain poorly characterised. Since the vector-borne nature of LSDV transmission is believed to have enabled the rapid geographic expansion of this virus, the lack of quantitative evidence on LSDV transmission has impeded effective control of the disease during the current epidemic. Obtaining high quality data on virus transmission by arthropods is challenging, and practical limitations often result in inadequate arthropod numbers or model hosts, limiting the transferability of experimental findings to the natural transmission scenario. We have addressed these limitations in this study. Using a highly representative bovine experimental model of lumpy skin disease we allowed four representative vector species (Aedes aegypti, Culex quinquefasciatus, Stomoxys calcitrans and Culicoides nubeculosus) to blood-feed on LSDV-inoculated cattle in order to examine the acquisition and retention of LSDV by these species in unprecedented detail. We found the probability of LSDV transmission from clinical cattle to vector correlated with disease severity. Subclinical disease was more common than clinical disease in the inoculated cattle, however the probability of vectors acquiring LSDV from subclinical animals was very low. All four potential vector species studied had a similar rate of acquisition of LSDV after feeding on the host, but Aedes aegypti and Stomoxys calcitrans retained the virus for a longer time, up to 8 days. There was no evidence of virus replication in the vector, consistent with mechanical rather than biological transmission. The parameters obtained in the in-vivo transmission experiments subsequently enabled enhanced modelling approaches to determine the basic reproduction number of LSDV in cattle mediated by each of the insect species. This was highest for Stomoxys calcitrans (19.1), C. nubeculosus (7.4), and Ae. aegypti (2.4), surprisingly indicating these three species are all potentially efficient transmitters of LSDV. These results reveal that currently applied LSDV control measures such as stamping out of all cattle on affected premises or insect control measures targeting single species need to be urgently reconsidered. Overall our studies have highlighted that the combination of highly relevant in-vivo experiments and mathematical modelling can be directly applied to devise evidence-based proportionate and targeted control programmes.

microbiology↗

Using the basic reproduction number to assess the risk of transmission of lumpy skin disease virus by biting insects

In recent years, lumpy skin disease virus (LSDV) has emerged as a major threat to cattle outside Africa, where it is endemic. Although evidence suggests that LSDV is transmitted by the bites of blood sucking arthropods, few studies have assessed the risk of transmission posed by particular vector species. Here this risk is assessed by calculating the basic reproduction number (R0) for transmission of LSDV by five species of biting insect: the stable fly, Stomoxys calcitrans, the biting midge, Culicoides nubeculosus, and three mosquito species, Aedes aegypti, Anopheles stephensi and Culex quinquefasciatus. Parameters relating to mechanical transmission of LSDV were estimated using new analyses of previously-published data from transmission experiments, while vector life history parameters were derived from the published literature. Uncertainty and sensitivity analyses were used to compute R0 for each species and to identify those parameters which influence its magnitude. Results suggest that S. calcitrans is likely to be the most efficient at transmitting LSDV, with Ae. aegypti also an efficient vector. By contrast, C. nubeculosus, An. stephensi, and Cx. quinquefasciatus are likely to be inefficient vectors of LSDV. However, there is considerable uncertainty associated with the estimates of R0, reflecting uncertainty in most of the constituent parameters. Sensitivity analysis suggests that future experimental work should focus on estimating the probability of transmission from insect to bovine and on the virus inactivation rate in insects.

epidemiology↗

Evidence of reduced viremia, pathogenicity and vector competence in a re-emerging European strain of bluetongue virus serotype 8 in sheep

The outbreak of bluetongue virus (BTV) serotype 8 (BTV-8) during 2006-2009 in Europe was the most costly epidemic of the virus in recorded history. In 2015, a BTV-8 strain re-emerged in France which has continued to circulate since then. To examine anecdotal reports of reduced pathogenicity and transmission efficiency, we investigated the infection kinetics of a 2007 UK BTV-8 strain alongside the re-emerging BTV-8 strain isolated from France in 2017. Two groups of eight BTV-naive British mule sheep were inoculated with 5.75 log10TCID50 ml-1 of either BTV-8 strain. BTV RNA was detected by 2 dpi in both groups with peak viremia occurring between 5-9 dpi. A significantly greater amount of BTV RNA was detected in sheep infected with the 2007 strain (6.0-8.8 log10 genome copies mL-1) than the re-emerging BTV-8 strain (2.9-7.9 log10 genome copies mL-1). All infected sheep developed BTV-specific antibodies by 9 dpi. BTV was isolated from 2 dpi to 12 dpi for 2007 BTV-8-inoculated sheep and from 5 to 10 dpi for sheep inoculated with the remerging BTV-8. In Culicoides sonorensis feeding on the sheep over the period 7-12 dpi, vector competence was significantly higher for the 2007 strain than the re-emerging strain. Both the proportion of animals showing moderate (as opposed to mild or no) clinical disease (6/8 vs 1/8) and the overall clinical scores (median 5.25 vs 3) were significantly higher in sheep infected with the 2007 strain, compared to those infected with the re-emerging strain. However, one sheep infected with the re-emerging strain was euthanized at 16 dpi having developed severe lameness. This highlights the potential of the re-emerging BTV-8 to still cause illness in naive ruminants with concurrent costs to the livestock industry.\n\nSummaryThe re-emerging Bluetongue virus serotype 8 still presents a threat to naive ruminants in Europe despite reduced virulence

epidemiology↗