Fruit Bats Research Articles

In silico screening of herbal phytochemicals to develop a Rasayana for immunity against Nipah virus

BackgroundThe first emergence of the Nipah virus (NiV) in 1998 from Malaysia became a major concern when it came to light and resurfaced on different occasions thereafter. NiV is a bat-borne zoonotic and pleomorphic virus that causes severe infection in human and animal hosts. Studies revealed fruit bats are the major reservoirs as natural hosts and pigs as intermediate hosts for the spread of this infection. This became a major concern as the disease was characterized by high pathogenicity varying from 40% to 80% depending on its acuteness. Moreover, the solemnity lies in the fact that the infection transcends from being a mere mild illness to an acute respiratory infection leading to fatal encephalitis with a reportedly high mortality rate. Currently, there is no treatment or vaccine available against the NiV. Many antiviral drugs have been explored and developed but with limited efficacy. MethodologyIn search of high-affinity ayurvedic alternatives, we conducted a pan-proteome in silico exploration of the NiV proteins for their interaction with the best-suited phytoconstituents. The toxicity prediction of thirty phytochemicals based on their LD50 value identified thirteen potential candidates. Molecular docking studies of those thirteen phytochemicals with five important NiV proteins identified Tanshinone I as the potential compound with a high binding affinity. ResultsThe pharmacokinetics and pharmacodynamics studies also aided in determining the absorption, distribution, metabolism, excretion, and toxicity of the selected phytoconstituent. Interestingly, docking studies also revealed Rosmariquinone as a potent alternative to the antiviral drug Remdesivir binding the same pocket of RNA-dependent RNA polymerase of the NiV. A molecular dynamics simulation study of the surface glycoprotein of NiV against Tanshinone I showed a stable complex formation and significant allosteric changes in the protein structure, implying that these phytochemicals could be a natural alternative to synthetic drugs against NiV. ConclusionThis study provides preliminary evidence based on in silico analysis that the herbal molecules showed an effect against NiV. However, it is essential to further evaluate the efficacy of this approach through cell–based experiments, organoid models, and eventually clinical trials.

The Era of Molecular Biology: Diagnostics for Nipah Virus

Abstract: Nipah virus (NiV) is an emerging pathogen that, unlike other priority pathogens identified by the WHO, is endemic to Southeast Asia. It is most commonly transmitted through exposure to saliva or excrement from the Pteropus fruit bat or direct contact with intermediate animal hosts, such as pigs. NiV infection causes severe febrile encephalitic disease and/or respiratory disease; treatment options are limited to supportive care. The serological and nucleic acid amplification techniques have been developed for NiV and are used in laboratory settings, including some early multiplex panels for differentiation of NiV infection. The rural and remote nature of NiV outbreak settings, there remains a need for rapid diagnostic tests that can be implemented at the point of care. Additionally, more reliable assays for surveillance of communities and livestock will be vital to achieving a better understanding of the fruit bat host and transmission risk to other intermediate hosts, enabling the implementation to outbreak prevention and the management of this NiV. An improved understanding of NiV viral diversity and infection kinetics or dynamics will be central to the development of new diagnostics to enable effective validation and external quality assessments

Cannabis sativa: 2023-Outbreak and Re-emergence of Nipah virus (NiV) in India: Role of Hemp oil

This review paper highlights and updates the outbreak of Nipah virus (NiV), an emerging zoonotic bat borne virus that can cause severe respiratory illness and deadly encephalitis in humans. Nipah virus (NiV) outbreak was first reported in 1998 from Malaysia and then recorded in Bangladesh, India, Philippines, Singapore and Thailand. A recent fifth outbreak of Nipah virus (NiV) during August-September 2023 in Kerala State, India brought this emerging-re-emerging virus into the spotlight again. Due to the lack of vaccines and drugs with proven effectiveness against Nipah virus (NiV), treatment of patients is limited to supportive and prophylactic. Fruit bats are the main reservoir for this virus, which can cause disease in humans and animals. Nipah virus (NiV) can be transmitted from bats or livestock to humans, typically via contaminated food (fruit or raw date palm sap), and person-to-person through respiratory secretions. Hemp seed oil has gained remarkable popularity due to its perceived therapeutic properties, particularly antiviral properties for potential health benefits. During the recent outbreak of Nipah virus (NiV), the local traditional healers in India used hemp oil as the mouth wash for controlling throat infections, head ache, vomiting and suggested for the consumption of hemp seeds and oil as the functional food. However, clinical trials and scientific data supporting antiviral activity of Cannabis oil (CBD oil) against Nipah virus (NiV) is lacking. Therefore, further research should focus on exploring the molecular mechanisms of hemp oil against Nipah virus (NiV) is warranted. Multicenter clinical trials should be performed to validate the efficacy of hemp oil alone or in the form of formulations for the treatment of viral infections.

Antiviral responses in a Jamaican fruit bat intestinal organoid model of SARS-CoV-2 infection

Bats are natural reservoirs for several zoonotic viruses, potentially due to an enhanced capacity to control viral infection. However, the mechanisms of antiviral responses in bats are poorly defined. Here we established a Jamaican fruit bat (JFB, Artibeus jamaicensis) intestinal organoid model of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Upon infection with SARS-CoV-2, increased viral RNA and subgenomic RNA was detected, but no infectious virus was released, indicating that JFB organoids support only limited viral replication but not viral reproduction. SARS-CoV-2 replication was associated with significantly increased gene expression of type I interferons and inflammatory cytokines. Interestingly, SARS-CoV-2 also caused enhanced formation and growth of JFB organoids. Proteomics revealed an increase in inflammatory signaling, cell turnover, cell repair, and SARS-CoV-2 infection pathways. Collectively, our findings suggest that primary JFB intestinal epithelial cells mount successful antiviral interferon responses and that SARS-CoV-2 infection in JFB cells induces protective regenerative pathways.

Structural insights on the nucleoprotein C-terminal domain of Měnglà virus.

Filoviruses depend on the nucleoprotein (NP) to accomplish multiple functions during the viral life cycle. NP is the most abundantly expressed viral protein in infected cells and the main component of the viral nucleocapsid. It can be structurally divided into amino- and carboxy- terminal domains (NTD and CTD). The NTD can homo-oligomerize to interact and protect the (-) ssRNA genome, forming long helical structures. The flexible CTD is responsible for the binding of other nucleocapsid proteins and is involved in the formation of inclusion bodies (IBs)-the cytoplasmic sites of nucleocapsid formation and genome replication. The CTD ends in a ~100-residue globular tail. Měnglà virus (MLAV) is the only member of the new Dianlovirus genus within the Filoviridae family. Their differential characteristics and the possibility of becoming a threat for human health justify the interest in better understanding of its structure and function. In this work, we present the structure of the globular tail of the MLAV NP CTD, showing an overall conformation closely related to that previously reported for the equivalent NP region in MARV. Moreover, analyses of the CTD-CTD interactions in the crystal asymmetric unit revealed a higher-order helicoidal structure. Mutational studies underscore the crucial role of a number of residues, located at the CTD-CTD contact interface, for IB formation. Site-directed mutagenesis of amino acids L653 and F687, involved in the formation of these helicoidal assemblies, abrogate the growth of IBs when the full-length MLAV NP was ectopically expressed in cells. Our findings confirm the role of NP CTD in IB formation, also for MLAV, and focus the attention on particular residues as starting point for further analysis.IMPORTANCEFiloviruses are the causative agents of severe and often fatal hemorrhagic disease in humans. Měnglà virus (MLAV) is a recently reported filovirus, isolated from fruit bats that is capable to replicate in human cells, representing a potential risk for human health. An in-depth structural and functional knowledge of MLAV proteins is an essential step for antiviral research on this virus that can also be extended to other emerging filoviruses. In this study, we determined the first crystal structures of the C-terminal domain (CTD) of the MLAV nucleoprotein (NP), showing important similarities to the equivalent domain in MARV. The structural data also show that the NP CTD has the ability to form large helical oligomers that may participate in the control of cytoplasmic inclusion body formation during viral replication.

Pteropus vampyrus TRIM40 Is an Interferon-Stimulated Gene That Antagonizes RIG-I-like Receptors.

Nipah virus (NiV; genus: Henipavirus; family: Paramyxoviridae) naturally infects Old World fruit bats (family Pteropodidae) without causing overt disease. Conversely, NiV infection in humans and other mammals can be lethal. Comparing bat antiviral responses with those of humans may illuminate the mechanisms that facilitate bats' tolerance. Tripartite motif proteins (TRIMs), a large family of E3-ubiquitin ligases, fine-tune innate antiviral immune responses, and two human TRIMs interact with Henipavirus proteins. We hypothesize that NiV infection induces the expression of an immunosuppressive TRIM in bat, but not human cells, to promote tolerance. Here, we show that TRIM40 is an interferon-stimulated gene (ISG) in pteropodid but not human cells. Knockdown of bat TRIM40 increases gene expression of IFNβ, ISGs, and pro-inflammatory cytokines following poly(I:C) transfection. In Pteropus vampyrus, but not human cells, NiV induces TRIM40 expression within 16 h after infection, and knockdown of TRIM40 correlates with reduced NiV titers as compared to control cells. Bats may have evolved to express TRIM40 in response to viral infections to control immunopathogenesis.

Regulatory T cell-like response to SARS-CoV-2 in Jamaican fruit bats (Artibeus jamaicensis) transduced with human ACE2.

Insectivorous Old World horseshoe bats (Rhinolophus spp.) are the likely source of the ancestral SARS-CoV-2 prior to its spillover into humans and causing the COVID-19 pandemic. Natural coronavirus infections of bats appear to be principally confined to the intestines, suggesting fecal-oral transmission; however, little is known about the biology of SARS-related coronaviruses in bats. Previous experimental challenges of Egyptian fruit bats (Rousettus aegyptiacus) resulted in limited infection restricted to the respiratory tract, whereas insectivorous North American big brown bats (Eptesicus fuscus) showed no evidence of infection. In the present study, we challenged Jamaican fruit bats (Artibeus jamaicensis) with SARS-CoV-2 to determine their susceptibility. Infection was confined to the intestine for only a few days with prominent viral nucleocapsid antigen in epithelial cells, and mononuclear cells of the lamina propria and Peyer's patches, but with no evidence of infection of other tissues; none of the bats showed visible signs of disease or seroconverted. Expression levels of ACE2 were low in the lungs, which may account for the lack of pulmonary infection. Bats were then intranasally inoculated with a replication-defective adenovirus encoding human ACE2 and 5 days later challenged with SARS-CoV-2. Viral antigen was prominent in lungs for up to 14 days, with loss of pulmonary cellularity during this time; however, the bats did not exhibit weight loss or visible signs of disease. From day 7, bats had low to moderate IgG antibody titers to spike protein by ELISA, and one bat on day 10 had low-titer neutralizing antibodies. CD4+ helper T cells became activated upon ex vivo recall stimulation with SARS-CoV-2 nucleocapsid peptide library and exhibited elevated mRNA expression of the regulatory T cell cytokines interleukin-10 and transforming growth factor-β, which may have limited inflammatory pathology. Collectively, these data show that Jamaican fruit bats are poorly susceptible to SARS-CoV-2 but that expression of human ACE2 in their lungs leads to robust infection and an adaptive immune response with low-titer antibodies and a regulatory T cell-like response that may explain the lack of prominent inflammation in the lungs. This model will allow for insight of how SARS-CoV-2 infects bats and how bat innate and adaptive immune responses engage the virus without overt clinical disease.

First investigation of blood parasites of bats in Burkina Faso detects Hepatocystis parasites and infections with diverse Trypanosoma spp.

Bats are hosts to a large diversity of eukaryotic protozoan blood parasites that comprise species of Trypanosoma and different haemosporidian parasite taxa and bats have played an important role in the evolutionary history of both parasite groups. However, bats in several geographical areas have not been investigated, including in Burkina Faso, where no information about malaria parasites and trypanosomes of bats exists to date.In this study, we collected data on the prevalence and the phylogenetic relationships of protozoan blood parasites in nine different bat species in Burkina Faso. Hepatocystis parasites were detected in two species of epauletted fruit bats, and a relatively high diversity of trypanosome parasites was identified in five bat species. The phylogenetic analyses recovered the trypanosome parasites of the bat species Rhinolophus alcyone and Nycteris hispida as close relatives of T. livingstonei, the trypanosome infections in Scotophilus leucogaster as closely related to the species T. vespertilionis and the trypanosomes from Pipistrellus nanulus and Epomophorus gambianus might present the species T. dionisii. These findings of the first investigation in Burkina Faso present a first snapshot of the diversity of protozoan blood parasites in bats in this country.

Viral interactions with host factors (TIM-1, TAM -receptors, Glut-1) are related to the disruption of glucose and ascorbate transport and homeostasis, causing the haemorrhagic manifestations of viral haemorrhagic fevers.

The haemorrhagic features of viral haemorrhagic fevers may be caused by common patterns of metabolic disturbances of the glucose and ascorbate homeostasis. Haemorrhages and vasculature disfunctions are a clinical feature not only of viral haemorrhagic fevers, but also in scurvy, diabetes and thrombotic microangiopathic haemolytic anaemia. Interestingly, the expression of glucose and ascorbate transporter Glut-1 on the erythrocyte membrane is associated with the inability to synthesize ascorbate and is restricted to that very species that are susceptible to Filoviruses (primates, humans and fruit bats). Glut-1 may play a pivotal role in haemorrhagic fever pathogenesis. TIM-1 and TAM receptors have been recognized to enhance entry of Ebola, Lassa and Dengue viruses and viral interferences with TIM-1 could disturb its function, disturbing the expression of Glut-1.

Evolution and divergence of the genetic lineage Desmodus rotundus/Artibeus lituratus of rabies virus in São Paulo State.

The last record of a rabies case caused by the dog-specific rabies virus (RABV) lineage in dogs or cats in São Paulo State was in 1998. From 2002 to 2021, 57 cases of rabies in these animals were reported, and the vast majority (51) were genetically characterized as belonging to theDesmodus rotundus/Artibeus lituratusRABV lineage. However, it is not currently possible to infer which of these bats is the source of infection by genome sequencing of RABV isolates. The aims of this study were (a) to characterize the Desmodus rotundus/Artibeus lituratus lineage to determine the relationships between the RABV lineages and each reservoir, (b) to assess the phylogeny and common ancestors of the RABV lineages found in D. rotundus and A. lituratus, and (c) to further understand the epidemiology and control of rabies. In this study, we genetically analyzed 70 RABV isolates from São Paulo State that were received by the Virology Laboratory of the Pasteur Institute of São Paulo between 2006 and 2015. Of these isolates, 33 were associated with the hematophagous batD. rotundus and 37 with the fruit bat A. lituratus. A genomic approach using phylogenetic analysis and nucleotide sequence comparisons demonstrated that these isolates belonged to the same genetic lineage of RABV. We also found that, in São Paulo State, the D. rotundus/A. lituratus lineage could be subdivided into at least four phylogenetic sublineages: two associated with D. rotundus and two with A. lituratus. These results are of importance for the epidemiological surveillance of rabies in São Paulo.

On the distribution of the Egyptian Fruit Bat Rousettus aegyptiacus in Saudi Arabia (Mammalia: Chiroptera)

New records of the Egyptian Fruit Bat (Rousettus aegyptiacus) from 14 sites situated in the north-western part of Saudi Arabia interconnect the previously known parts of the distributon range of this bat in Arabia and suggest its continuous occurrence in a belt of coastal regions and the Hijaz Mountains along the Red Sea. These data indicate that the fruit bats can occur in very small spots of fertile environment surrounded by arid rocks and deserts and use them as foraging and roosting habitats. The occurrence of R. aegyptiacus was also confirmed in most of the sites where it was suggested previously. The occurrence in Hail represents the most remote spot of the fruit bat presence in the Arabian Desert, situated more than 500 km from the closest seashore, and around 315 km from the closest locality of R. aegyptiacus reported previously. We consider this occurrence an overlooked but traditional part of R. aegyptiacus distribution, connected with the broad use of the Date Palms grown in the area continuously since antiquity.

Rise of Marburg virus in Africa: a call for global preparedness.

The Marburg virus disease (MVD) is caused by a rare RNA virus that can result in severe hemorrhagic fever in humans and other primates. The disease was first discovered in 1967 in Marburg Frankfurt in Germany and since then, sporadic cases have been reported in southeastern Africa. The Egyptian fruit bat is considered a reservoir for the virus, which can be transmitted through direct contact with infected bat or monkey tissue, bodily fluids, or contaminated objects. The Marburg virus disease shares clinical features with the Ebola virus disease, and there are no widely accepted vaccines or antiviral medications to treat it. The article provides an overview of Marburg virus (MARV) outbreaks in Africa, including the most recent outbreaks in Guinea, Ghana, Equatorial Guinea, and Tanzania. The authors discuss the recent outbreaks and the implications of the spread of MARV to Africa's healthcare systems. The authors also present key recommendations for both multicountry and global preparedness efforts in order to better prevent and respond to future MARV outbreaks and other viruses with an epidemic potential.

Where do Egyptian fruit bats fly when auditory and visual spatial information conflicts?

Egyptian fruit bats, Rousettus aegyptiacus, present a distinct opportunity to unravel the relative contributions of auditory and visual stimuli for navigation. This species has evolved lingual echolocation, but also uses rod vision to navigate. Echolocation and visual gaze are anchored to the head, but the bat's active control over sonar beam aim, ear, and eye position can influence sampling of sensory space. We investigated the relative weighting of echolocation and vision in free-flying Egyptian fruit bats. In this experiment, we used stereo IR video and microphone array recordings to quantify the bat’s trajectory, head direction and sonar beam as it flew to a landing perch. We introduced sensory conflict by equipping the bats with goggles fit with prisms that shifted visual images by 23 degrees to the left or right. In control trials, prisms were replaced with clear or light-blocking lenses. When bats were presented with conflicting visual and echolocation information, they flew in the direction of the prism shift and often missed the perch. Preliminary analyses of sonar beam aim suggests that their navigation is largely guided by vision. These findings underscore the dominant role of vision in bats that have also evolved auditory specializations to operate in darkness.

Chiropteran diversity and diet of fruit bats in a tropical dry forest of northern South America

Remnants of Tropical Dry Forest persist in urban and peri-urban areas and are essential for maintaining biodiversity and ecosystem services. However, the challenges facing the conservation of these respective forests have intensified with the encroachment of the urban frontier, mining activities, deforestation, and cattle ranching. In this context, our study aims to estimate the diversity of the order Chiroptera and characterize the diet of the family Phyllostomidae. This approach allows us to gain insights into the ecological dynamics and assess the status of Tropical Dry Forest fragments located within the urban and peri-urban areas of Cúcuta, Colombia. Field sampling was conducted from January to September 2018, with a total sampling effort of 2,160 hours/meter/net. Bats were sexed, morphometrically characterized, and had their feces collected for diet analysis before being tagged and released. We identified three families, nine genera, and 11 species. A total of 276 individuals were captured. Seven species were observed in the urban area and ten in the peri-urban zone; Artibeus lituratus and Carollia perspicillata were the most abundant species in both locations. The diet included seeds from the families Moraceae, Anacardiaceae, and Rosaceae. Our findings reveal that in areas with dense vegetation, such as peri-urban zones, frugivorous bats prefer to consume fruits of domesticated species, including economically significant fruits like guava and tomato. This dietary shift could alter seed dispersal patterns and the dynamics of the Tropical Dry Forest, highlighting the ecological importance of these flying mammals in ecosystem regeneration.

Monitoring fruit bat colonies could provide early warning for Nipah outbreaks

Monitoring fruit bat colonies could provide early warning for Nipah outbreaks

Viral interactions with host factors (TIM-1, TAM -receptors, Glut-1) are related to the disruption of glucose and ascorbate transport and homeostasis, causing the haemorrhagic manifestations of viral haemorrhagic fevers.

The haemorrhagic features of viral haemorrhagic fevers may be caused by common patterns of metabolic disturbances of the glucose and ascorbate homeostasis. Haemorrhages and vasculature disfunctions are a clinical feature not only of viral haemorrhagic fevers, but also in scurvy, diabetes and thrombotic microangiopathic haemolytic anaemia. Interestingly, the expression of glucose and ascorbate transporter Glut-1 on the erythrocyte membrane is associated with the inability to synthesize ascorbate and is restricted to that very species that are susceptible to Filoviruses (primates, humans and fruit bats). Glut-1 may play a pivotal role in haemorrhagic fever pathogenesis. TIM-1 and TAM receptors have been recognized to enhance entry of Ebola, Lassa and Dengue viruses and viral interferences with TIM-1 could disturb its function, disturbing the expression of Glut-1.

Viral maintenance and excretion dynamics of coronaviruses within an Egyptian rousette fruit bat maternal colony: considerations for spillover

Novel coronavirus species of public health and veterinary importance have emerged in the first two decades of the twenty-first century, with bats identified as natural hosts for progenitors of many coronaviruses. Targeted wildlife surveillance is needed to identify the factors involved in viral perpetuation within natural host populations, and drivers of interspecies transmission. We monitored a natural colony of Egyptian rousette bats at monthly intervals across two years to identify circulating coronaviruses, and to investigate shedding dynamics and viral maintenance within the colony. Three distinct lineages were detected, with different seasonal temporal excretion dynamics. For two lineages, the highest periods of coronavirus shedding were at the start of the year, when large numbers of bats were found in the colony. Highest peaks for a third lineage were observed towards the middle of the year. Among individual bat-level factors (age, sex, reproductive status, and forearm mass index), only reproductive status showed significant effects on excretion probability, with reproductive adults having lower rates of detection, though factors were highly interdependent. Analysis of recaptured bats suggests that viral clearance may occur within one month. These findings may be implemented in the development of risk reduction strategies for potential zoonotic coronavirus transmission.

Homoeopathy in NIPAH Virus

Nipah virus disease outbreak occurred in Kerala in the month of May 2018. It happened in Kerala again in September 2023. As on 13th September 2023, two unnatural deaths from Kozhikode district were suspected to be due to Nipah virus infection. Again in Sept 14, 2023, TOI reports that Kerala reported its 5th case. In the absence of a definitive cure for this viral disease, the article peeps through the homoeopathic lens & explores what it can offer to deal with this viral episode. The success of homoeopathy in COVID 19 again reiterates the fact that as homoeopathy was & is effective against viral infections; it is effective against Nipah virus disease also [2]. Nipah virus is an enveloped RNA virus that has been a major cause of encephalitis outbreaks with high mortality primarily in the Indo-Bangladesh regions. The first breakout was in Malaysia-Singapore that was related to contact with pigs & the outbreak in Phillipines associated with horse slaughter. Most other out breaks has affected the Indo- Bangladesh regions. Here, the outbreaks were associated with consumption of raw date palm sap contaminated by fruit bats & had a very high secondary attack rate [3].

Emergence of Marburg virus: a global perspective on fatal outbreaks and clinical challenges.

The Marburg virus (MV), identified in 1967, has caused deadly outbreaks worldwide, the mortality rate of Marburg virus disease (MVD) varies depending on the outbreak and virus strain, but the average case fatality rate is around 50%. However, case fatality rates have varied from 24 to 88% in past outbreaks depending on virus strain and case management. Designated a priority pathogen by the National Institute of Allergy and Infectious Diseases (NIAID), MV induces hemorrhagic fever, organ failure, and coagulation issues in both humans and non-human primates. This review presents an extensive exploration of MVD outbreak evolution, virus structure, and genome, as well as the sources and transmission routes of MV, including human-to-human spread and involvement of natural hosts such as the Egyptian fruit bat (Rousettus aegyptiacus) and other Chiroptera species. The disease progression involves early viral replication impacting immune cells like monocytes, macrophages, and dendritic cells, followed by damage to the spleen, liver, and secondary lymphoid organs. Subsequent spread occurs to hepatocytes, endothelial cells, fibroblasts, and epithelial cells. MV can evade host immune response by inhibiting interferon type I (IFN-1) synthesis. This comprehensive investigation aims to enhance understanding of pathophysiology, cellular tropism, and injury sites in the host, aiding insights into MVD causes. Clinical data and treatments are discussed, albeit current methods to halt MVD outbreaks remain elusive. By elucidating MV infection's history and mechanisms, this review seeks to advance MV disease treatment, drug development, and vaccine creation. The World Health Organization (WHO) considers MV a high-concern filovirus causing severe and fatal hemorrhagic fever, with a death rate ranging from 24 to 88%. The virus often spreads through contact with infected individuals, originating from animals. Visitors to bat habitats like caves or mines face higher risk. We tailored this search strategy for four databases: Scopus, Web of Science, Google Scholar, and PubMed. we primarily utilized search terms such as "Marburg virus," "Epidemiology," "Vaccine," "Outbreak," and "Transmission." To enhance comprehension of the virus and associated disease, this summary offers a comprehensive overview of MV outbreaks, pathophysiology, and management strategies. Continued research and learning hold promise for preventing and controlling future MVD outbreaks. GRAPHICAL ABSTRACT.

Long-Read Sequencing Reveals Rapid Evolution of Immunity- and Cancer-Related Genes in Bats.

Bats are exceptional among mammals for their powered flight, extended lifespans, and robust immune systems and therefore have been of particular interest in comparative genomics. Using the Oxford Nanopore Technologies long-read platform, we sequenced the genomes of two bat species with key phylogenetic positions, the Jamaican fruit bat (Artibeus jamaicensis) and the Mesoamerican mustached bat (Pteronotus mesoamericanus), and carried out a comprehensive comparative genomic analysis with a diverse collection of bats and other mammals. The high-quality, long-read genome assemblies revealed a contraction of interferon (IFN)-α at the immunity-related type I IFN locus in bats, resulting in a shift in relative IFN-ω and IFN-α copy numbers. Contradicting previous hypotheses of constitutive expression of IFN-α being a feature of the bat immune system, three bat species lost all IFN-α genes. This shift to IFN-ω could contribute to the increased viral tolerance that has made bats a common reservoir for viruses that can be transmitted to humans. Antiviral genes stimulated by type I IFNs also showed evidence of rapid evolution, including a lineage-specific duplication of IFN-induced transmembrane genes and positive selection in IFIT2. In addition, 33 tumor suppressors and 6 DNA-repair genes showed signs of positive selection, perhaps contributing to increased longevity and reduced cancer rates in bats. The robust immune systems of bats rely on both bat-wide and lineage-specific evolution in the immune gene repertoire, suggesting diverse immune strategies. Our study provides new genomic resources for bats and sheds new light on the extraordinary molecular evolution in this critically important group of mammals.