Bat Lyssavirus Research Articles

Bat Rabies in the Americas: Is Myotis the Main Ancestral Spreader?

The rabies virus (RABV) is the exclusive lyssavirus affecting both wild and domestic mammalian hosts in the Americas, including humans. Additionally, the Americas stand out as the sole region where bat rabies occurs. While carnivore rabies is being increasingly managed across the region, bats are emerging as significant reservoirs of RABV infection for humans and domestic animals. Knowledge of the bat species maintaining rabies and comprehending cross-species transmission (CST) and host shift processes are pivotal for directing surveillance as well as ecological research involving wildlife reservoir hosts. Prior research indicates that bat RABV CST is influenced by host genetic similarity and geographic overlap, reflecting host adaptation. In this study, we compiled and analyzed a comprehensive nucleoprotein gene dataset representing bat-borne RABV diversity in Argentina and the broader Americas using Bayesian phylogenetics. We examined the association between host genus and geography, finding both factors shaping the global phylogenetic structure. Utilizing a phylogeographic approach, we inferred CST and identified key bat hosts driving transmission. Consistent with CST determinants, we observed monophyletic/paraphyletic clustering of most bat genera in the RABV phylogeny, with stronger CST evidence between host genera of the same family. We further discuss Myotis as a potential ancestral spreader of much of RABV diversity.

Investigating the emergence of a zoonotic virus: phylogenetic analysis of European bat lyssavirus 1 in the UK.

European bat lyssavirus 1 (EBLV-1, Lyssavirus hamburg) is predominantly detected in serotine bats (Eptesicus serotinus) and is responsible for the majority of bat rabies cases in mainland Europe. A passive bat rabies surveillance scheme detected the virus in a serotine bat in the UK for the first time in October 2018. As of May 2024, 34 cases have been reported, 20 of which involved contact with an animal and 5 reported human contact. We investigated the emergence of EBLV-1 by undertaking comprehensive sequence analysis and Bayesian phylogenetics, based on complete virus genomes of 33 UK sequences and 108 sequences covering six countries in mainland Europe (1968-2023), including 21 French EBLV-1-positive RNA samples sequenced for this study. Sequence analysis revealed extreme similarity among UK EBLV-1 sequences (99.9%-100%), implying a single source of introduction rather than multiple independent introductions. Bayesian analysis revealed that the UK EBLV-1 sequences shared their most recent common ancestor with an EBLV-1 sequence from a serotine bat detected in Brittany, France, in 2001, with an estimated date of divergence of 1997. Within the UK sequences, the earliest divergence was estimated to occur in 2007. This study provides valuable insights into the molecular epidemiology of an emerging zoonotic pathogen and improved understanding of the risks posed to public and animal health.

Detection and Serological Evidence of European Bat Lyssavirus 1 in Belgian Bats between 2016 and 2018.

Lyssaviruses are neurotropic viruses capable of inducing fatal encephalitis. While rabies virus has been successfully eradicated in Belgium, the prevalence of other lyssaviruses remains uncertain. In this study, we conducted a survey on live animals and passive surveillance to investigate the presence of lyssaviruses in Belgium. In 2018, a total of 113 saliva samples and 87 blood samples were collected from bats. Saliva was subjected to RT-qPCR to identify lyssavirus infections. Additionally, an adapted lyssavirus neutralisation assay was set up for the detection of antibodies neutralising EBLV-1 in blood samples. Furthermore, we examined 124 brain tissue samples obtained from deceased bats during passive surveillance between 2016 and 2018. All saliva samples tested negative for lyssaviruses. Analysis of the blood samples uncovered the presence of lyssavirus-neutralising antibodies in five bat species and 32% of samples with a wide range depending on bat species, suggesting past exposure to a lyssavirus. Notably, EBLV-1 was detected in brain tissue samples from two Eptesicus serotinus specimens collected in 2016 near Bertrix and 2017 near Étalle, confirming for the first time the presence of EBLV-1 in Belgium and raising awareness of the potential risks associated with this species of bats as reservoirs of the virus.

Rabies virus circulation in a highly diverse bat assemblage from a high-risk area for zoonoses outbreaks in the Brazilian Amazon

Bats are the second most diverse order of mammals and play a central role in ecosystem dynamics. They are also important reservoirs of potentially zoonotic microorganisms, of which rabies virus is the most lethal among the bat-transmitted zoonotic pathogens. Importantly, recent outbreaks of human rabies have been reported from the Brazilian Amazon. Here we present a survey of bat species and rabies virus (RABV) circulation in a bat assemblage in the Marajó region, northern Brazil. Using data from mist-net captures and bioacoustic sampling, 56 bat species were recorded along the Jacundá River basin over a 10-day expedition in November 2022. For the investigation of RABV, we used the direct fluorescent antibody test (DFAT) and the rapid fluorescent focus inhibition test (RFFIT). In total, 159 bat individuals from 22 species were investigated for RABV. Five adults of the common vampire bat, Desmodus rotundus, showed RABV-specific antibodies in serum samples. Additionally, we report on local residents with injuries caused by D. rotundus bites and the occurrence of colonies of non-hematophagous bats from different species roosting inside human residences. This scenario raises concerns about the risks of new cases of human rabies and other zoonotic diseases associated with bats in the region and highlights the need for epidemiological surveillance and mitigation measures to prevent outbreaks of emerging infectious diseases.

A Preliminary Study on Bat Lyssavirus in Assam, India

A Preliminary Study on Bat Lyssavirus in Assam, India

Cross-Neutralization Activities of Antibodies against 18 Lyssavirus Glycoproteins.

Some lyssaviruses, including the rabies virus (RABV), cause lethal neurological symptoms in humans. However, the efficacy of commercial vaccines has only been evaluated against RABV. To assess cross-reactivity among lyssaviruses, including RABV, sera from rabbits inoculated with human and animal RABV vaccines and polyclonal antibodies from rabbits immunized with expression plasmids of the glycoproteins of all 18 lyssaviruses were prepared, and cross-reactivity was evaluated via virus-neutralization tests using Duvenhage lyssavirus (DUVV), European bat lyssavirus-1 (EBLV-1), Mokola lyssavirus (MOKV), Lagos bat lyssavirus (LBV), and RABV. The sera from rabbits inoculated with RABV vaccines showed cross-reactivity with EBLV-1 and DUVV, both belonging to phylogroup I. However, reactivity with MOKV and LBV in phylogroup II was notably limited or below the detection level. Next, we compared the cross-reactivity of the polyclonal antibodies against all lyssavirus glycoproteins. Polyclonal antibodies had high virus-neutralization titers against the same phylogroup but not different phylogroups. Our findings indicate that a new vaccine should be developed for pre- and post-exposure prophylaxis against lyssaviral infections.

Presencia del virus de la rabia en murciélagos no hematófagos en México

The presence of the rabies virus and antibodyes in bats from the Americas is mainly associated with hematophagous species; however, this virus has also been detected with low frequency in bats with other feeding habits. The same thing happens in Mexico, although there is no updated information on the species that have been infected by this virus. Due to the public health implications of the subject, in this study we explore how the presence of the rabies virus is related to eating habits, the family to which they belong, the size of the distribution area and the type of refuge used by bats. Based on a review of the scientific literature published from 1954 to 2015, seven families, 24 genera, and 40 species of non-hematophagous bats that have been detected with rabies virus in Mexico. Most are insectivorous (63%) and belong to the Phyllostomidae and Vespertilionidae families (68%). The presence of rabies is positively and significantly related to the number of species per family (r = 0.9, p < 0.005) and type of feeding habit (r = 0.97, p < 0.002) but is not related to the size of its distribution area (r = 0.2, p = 0.2). Cases of rabies in non-hematophagous species in Mexico are rare, and do not represent a risk of transmission to humans.

Retraction: Prevalence and public health significance of rabies virus in bats in the North Region of Cameroon.

Retraction: Prevalence and public health significance of rabies virus in bats in the North Region of Cameroon.

Field testing Australian bat lyssavirus risk communication resources.

Australian bat lyssavirus (ABLV) is a fatal zoonosis, which can be transmitted to humans through scratches or bites from infected bats. Currently, there is a lack of research evaluating risk communication resources about ABLV or the dangers from handling bats. The purpose of this study was to field test resources aimed at educating the public about risks to humans and bats from human-bat interaction, then update these resources based upon feedback to ensure they were relevant and appropriately targeted to the public. Thirteen semi-structured interviews with a purposive sample of participants chosen for maximum variation of age and sex were conducted. Two investigators analysed the data independently using a deductive approach and then came to consensus by discussion. The main themes were a wide-ranging level of knowledge and opinions about bats, the resources having an effect on people, and messaging in relation to children and pets being particularly important. This study highlighted the complexities of risk communication to a broad audience with varied experience and knowledge about bats, and the importance of evaluation prior to implementation to ensure risk communication is relevant and appealing to the intended audience. SO WHAT?: Field testing of health education material prior to implementation is an effective way to ensure key messages are understood, and is important when communicating about fatal but preventable zoonoses such as ABLV.

Structural Determination of the Australian Bat Lyssavirus Nucleoprotein and Phosphoprotein Complex.

Australian bat lyssavirus (ABLV) shows similar clinical symptoms as rabies, but there are currently no protein structures available for ABLV proteins. In lyssaviruses, the interaction between nucleoprotein (N) and phosphoprotein (N) in the absence of RNA generates a complex (N0P) that is crucial for viral assembly, and understanding the interface between these two proteins has the potential to provide insight into a key feature: the viral lifecycle. In this study, we used recombinant chimeric protein expression and X-ray crystallography to determine the structure of ABLV nucleoprotein bound to residues 1-40 of its phosphoprotein chaperone. Comparison of our results with the recently generated structure of RABV CVS-11 N0P demonstrated a highly conserved interface in this complex. Because the N0P interface is conserved in the lyssaviruses of phylogroup I, it is an attractive therapeutic target for multiple rabies-causing viral species.

Evaluating the benefit of serology during potential Australian bat lyssavirus and rabies post-exposure prophylaxis

Post-exposure prophylaxis (PEP) for potential lyssavirus exposures consists of wound management, rabies vaccination and may include rabies immunoglobulin (RIG). Rabies serology is sometimes indicated if there is risk of PEP failure. ObjectivesEvaluate the benefit of serology by indication. MethodsChart review of potential lyssavirus exposures managed at a Public Health Unit (June 2015 – December 2022) where serology was requested was conducted. The proportion of non-therapeutic titres was compared by sex, age, Indigenous status, serology indication, and whether RIG was given. Results46 notifications with serology were included. Males (5/19) and people over 40 (3/16) were more likely to demonstrate a non-therapeutic response. 2/3 of cases where vaccine doses were not given in the deltoid were non-therapeutic. The rate of non-therapeutic titres was similar for RIG given into the ipsilateral arm (2/11) and given excess RIG for weight (1/4). Although this small sample was inconclusive in isolation, it was also noted that all cases who did not receive RIG had therapeutic serology, whereas 6/35 of those receiving RIG had non-therapeutic serology. ConclusionsThis study supports broader literature questioning the utility of systemic RIG administration as likely limited and potentially detrimental considering the increased risk of immune interference. Implications for public healthHighlights a need to review Australian national guidelines to align with World Health Organization advice recommending local RIG administration only.

Prevalence and public health significance of rabies virus in bats in the North Region of Cameroon.

Rabies is a zoonotic disease of all warm-blooded animals including humans. There is a paucity of data on the status of rabies in wild animals in Cameroon and the disease is endemic in the country with dogs being the main source of transmission. Bat habitats are widespread in Cameroon, but there is limited information on the prevalence of rabies in bats, and their role of as potential reservoirs of rabies virus. A cross sectional study was carried out to estimate the prevalence and to assess risk factors of rabies virus in bats in the North Region of Cameroon. A total of 212 bats belonging to three families (Pteropodidae, Vespertilionidae and Molossidae) and 5 species were sampled in 7 localities in the North Region of Cameroon and were tested for rabies virus antigen using direct Immunofluorescence Test (IFA). Overall, 26.9% (57/212) of the bats collected showed an IFA positive reaction. The prevalence was significantly higher (P<0.05) in adult bats (33.3% (36/108)) compared to young individuals (20.2%; 21/104). The main risk factors identified in the study for human exposure to bats were gender (Male), religion (Christianity), localities (Babla and Lagdo), the practice of bat hunting, bat consumption, unawareness of bat rabies and cohabitation with bats in close proximity. The study revealed the first evidence of Lyssavirus in bats in Cameroon. This finding showed that bat rabies are real and represents a potential public health concern in communities with bat habitats in the North Region of Cameroon. Enhancing the level of public awareness and health education on the potential of bats as reservoirs of Lyssavirus in Cameroon as well as the integration of the "One Health" approach for effective management of animal and human rabies should be emphasized.

A rabies-related lyssavirus from a Nycticeinops schlieffeni bat with neurological signs, South Africa.

We report the coding-complete sequence of a lyssavirus, provisionally designated Phala bat lyssavirus (PBLV), characterized using a metagenomics approach. PBLV was identified in a Nycticeinops schlieffeni bat that exhibited neurological signs and died within 24 hours of admission to a wildlife rehabilitation center in Phalaborwa, South Africa.

Evaluation of Taxonomic Characteristics of Matlo and Phala Bat Rabies-Related Lyssaviruses Identified in South Africa.

We report the genetic characterization of two potentially novel rabies-related lyssaviruses identified from bats in Limpopo province, South Africa. Matlo bat lyssavirus (MBLV) was identified in two Miniopterus natalensis (Natal long-fingered) bats in 2015 and 2016, and Phala bat lyssavirus (PBLV) was identified in a Nycticeinops schlieffeni (Schlieffen's) bat in 2021. The distribution of both of these bat species is largely confined to parts of Africa, with limited reports from the Arabian Peninsula. MBLV and PBLV were demonstrated to group with the unassigned and phylogroup I lyssaviruses, respectively. MBLV was most closely related to Lyssavirus caucasicus (WCBV), whereas PBLV was most closely related to Lyssavirus formosa (TWBLV-1) and Taiwan bat lyssavirus 2 (TWBLV-2), based on analysis of the N and G genes, the concatenated N + P + M + G + L coding sequence, and the complete genome sequence. Based on our analysis, MBLV and WCBV appeared to constitute a phylogroup separate from Lyssavirus lleida (LLEBV) and Lyssavirus ikoma (IKOV). Analysis of the antigenic sites suggests that PBLV will likely be serologically distinguishable from established lyssaviruses in virus-neutralization tests, whereas MBLV appeared to be antigenically highly similar to WCBV. Taken together, the findings suggested that, while PBLV is likely a new lyssavirus species, MBLV is likely related to WCBV.

Communicating the risks of handling bats: analysing approaches used by Australian stakeholders in the context of Australian bat lyssavirus.

Australian bat lyssavirus (ABLV) is a member of the Lyssavirus genus of the Rhabdoviridae family and is found in Australian bat species. It is of public health concern because of the rabies-like syndrome it causes in humans, resulting in government health and wildlife agencies using varied communication approaches to inform targeted audiences about zoonotic risks associated with handling bats. Despite these warnings, the number of reports of human-bat interactions remains high. This paper details a survey conducted to analyse the approaches utilised by a range of stakeholders to educate and communicate warnings to their target audiences. The survey focused on identifying the target audiences, communication methods used, along with the message frequency, content, and perceived effectiveness. Analysis of the top three messages delivered by stakeholders revealed that over half were information-focused messages and over a third, instruction-focused. Stakeholders identified the need to balance messaging about bat handling risks with information regarding the vulnerable status of bats and their environmental significance. Whilst the most common and (perceived) effective method of communication was one-on-one discussions, it was also identified to be ineffective for targeting mass audiences leading stakeholders to recognise the need to adapt to more efficient means of communication. The outcomes of this study may be useful to improve risk communication strategies regarding ABLV in Australia.

Phylogeographic Aspects of Bat Lyssaviruses in Europe: A Review.

During the last few decades, bat lyssaviruses have become the topic of intensive molecular and epidemiological investigations. Since ancient times, rhabdoviruses have caused fatal encephalitis in humans which has led to research into effective strategies for their eradication. Modelling of potential future cross-species virus transmissions forms a substantial component of the recent infection biology of rabies. In this article, we summarise the available data on the phylogeography of both bats and lyssaviruses in Europe and the adjacent reg ions, especially in the contact zone between the Palearctic and Ethiopian realms. Within these zones, three bat families are present with high potential for cross-species transmission and the spread of lyssaviruses in Phylogroup II to Europe (part of the western Palearctic). The lack of effective therapies for rabies viruses in Phylogroup II and the most divergent lyssaviruses generates impetus for additional phylogenetic and virological research within this geographical region.

Discovery of a novel bat lyssavirus in a Long-fingered bat (Myotis capaccinii) from Slovenia.

Lyssaviruses are the causative agents of rabies, a zoonotic, fatal disease that is thought to be ancestral to bats. In the last decade, the detection of bat associated lyssaviruses is increasing also in Europe. Within a retrospective bat associated lyssavirus surveillance study a total of 225 dead bats of 21 bat species were collected in Slovenia between 2012 and 2019 and tested by specific real-time RT-PCR method. The first lyssavirus positive sample in bats in Slovenia was detected using the real-time RT-PCR, the fluorescent antibody test, and next generation sequencing, while the rabies tissue culture inoculation test was unsuccessful due to sample degradation and storage conditions. The nearly complete genome of Divača bat lyssavirus from Slovenia consists of 11,871 nucleotides and reflects the characteristic gene organization known for lyssaviruses, encoding the five viral proteins. Phylogenetic analysis of Divača bat lyssavirus revealed that it belongs to phylogroup I lyssaviruses and is most closely related to Kotalahti bat lyssavirus (KBLV) with 87.20% nucleotide and 99.22% amino acid identity. Together with KBLV, Khujand virus, European bat lyssavirus 2, Bakeloh bat lyssavirus, and Aravan virus, Divača bat lyssavirus was detected in the genus Myotis suggesting its key role in the transmission and maintenance of certain lyssaviruses.

Emergence, Tropism, Disease, and Treatment of Australian Bat Lyssavirus Infections in Humans.

Australian bat lyssavirus (ABLV) is a negative-sense, single-stranded RNA rhabdovirus capable of causing fatal acute encephalitis in humans with similar pathogenesis to its closest serologic relative, rabies virus (RABV). In this review, we describe emergence and classification of ABLV, its known virology, reservoirs, and hosts, as well as both the pathogenesis and treatment approaches currently employed for presumed infections. ABLV was first identified in New South Wales, Australia in 1996 and emerged in humans months later in Queensland, Australia. Only five known bat reservoirs, all of which fall within the Pteropus and Saccolaimus genera, have been identified to date. Although ABLV antigens have been identified in bats located outside of Australia, the three known human ABLV infections to date have occurred within Australia. As such, there remains a potential for ABLV to expand its presence within and beyond Australia. ABLV infections are currently treated as if they were RABV infections by administering neutralizing antibodies against RABV at the site of the wound and employing the rabies vaccine upon possible exposures. Due to its recent emergence, there is still much left unknown about ABLV, posing concerns with how to safely and effectively address current and future ABLV infections.

Notifications of suspected rabies exposure increased in Finland: 26 years of one health surveillance, 1995–2020

Background Finland is a rabies virus-free country since 1991. Notification of suspected cases of rabies exposures, leading to post-exposure prophylaxis, is mandatory. We characterised suspected cases of rabies exposure, analysed animal surveillance data and calculated costs for vaccine and immunoglobulin and treatment to estimate the financial burden of rabies control in Finland. Methods The incidence rate ratios of suspected cases of rabies exposure were calculated from Finnish Infectious Disease Registry and Statistics Finland data. Animal surveillance data were obtained from the Finnish Food Authority’s registries. Calculation of costs were based on the medical and treatment costs of rabies control. Results In 2007, one human rabies infection linked to a dog bite in the Philippines and rabies infection in a dog imported from India were diagnosed in Finland. In 2009, 2016 and 2017, lyssaviruses were found in bats. Notifications of suspected rabies exposures increased during 2007–2019. Two-thirds of the exposures occurred abroad, mainly in Asian and African countries. Bats were the most frequent domestic exposing animal. The import of vaccine and immunoglobulin doses increased. The annual cost of Finnish rabies control is estimated to be over €1.65 million. Conclusions Increased awareness of rabies and bat lyssavirus infections probably increased post-exposure prophylaxis and reporting. Travellers need country-specific guidance on how to prevent exposures, and citizens need instructions on animal imports and how to handle bats.

Transcriptomic responses of bat cells to European bat lyssavirus 1 infection under conditions simulating euthermia and hibernation

BackgroundCoevolution between pathogens and their hosts decreases host morbidity and mortality. Bats host and can tolerate viruses which can be lethal to other vertebrate orders, including humans. Bat adaptations to infection include localized immune response, early pathogen sensing, high interferon expression without pathogen stimulation, and regulated inflammatory response. The immune reaction is costly, and bats suppress high-cost metabolism during torpor. In the temperate zone, bats hibernate in winter, utilizing a specific behavioural adaptation to survive detrimental environmental conditions and lack of energy resources. Hibernation torpor involves major physiological changes that pose an additional challenge to bat-pathogen coexistence. Here, we compared bat cellular reaction to viral challenge under conditions simulating hibernation, evaluating the changes between torpor and euthermia.ResultsWe infected the olfactory nerve-derived cell culture of Myotis myotis with an endemic bat pathogen, European bat lyssavirus 1 (EBLV-1). After infection, the bat cells were cultivated at two different temperatures, 37 °C and 5 °C, to examine the cell response during conditions simulating euthermia and torpor, respectively. The mRNA isolated from the cells was sequenced and analysed for differential gene expression attributable to the temperature and/or infection treatment. In conditions simulating euthermia, infected bat cells produce an excess signalling by multitude of pathways involved in apoptosis and immune regulation influencing proliferation of regulatory cell types which can, in synergy with other produced cytokines, contribute to viral tolerance. We found no up- or down-regulated genes expressed in infected cells cultivated at conditions simulating torpor compared to non-infected cells cultivated under the same conditions. When studying the reaction of uninfected cells to the temperature treatment, bat cells show an increased production of heat shock proteins (HSPs) with chaperone activity, improving the bat’s ability to repair molecular structures damaged due to the stress related to the temperature change.ConclusionsThe lack of bat cell reaction to infection in conditions simulating hibernation may contribute to the virus tolerance or persistence in bats. Together with the cell damage repair mechanisms induced in response to hibernation, the immune regulation may promote bats’ ability to act as reservoirs of zoonotic viruses such as lyssaviruses.