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International Journal of Environmental... Jan 2024Rabies, caused by the Lyssavirus genus, is a highly lethal zoonotic disease transmitted by animals such as bats and domestic and wild carnivores to humans, claiming...
Rabies, caused by the Lyssavirus genus, is a highly lethal zoonotic disease transmitted by animals such as bats and domestic and wild carnivores to humans, claiming nearly 100% of lives. In Brazil, recent evidence suggests an increasing role of bats in human deaths from rabies, particularly in the Amazon region. This neglected tropical disease disproportionately affects impoverished and vulnerable populations in rural areas, where approximately 80% of human cases are concentrated. This article presents research conducted in riverine communities of the Tapajós/Arapiuns Extractive Reserve in Brazil to combat rabies in September 2022. The study adopted a participatory and collaborative approach, involving community members, healthcare professionals, and educators. Prioritizing proactive interventions, the health team administered prophylactic vaccinations to 30 individuals residing in communities exposed to the Lyssavirus. Educational activities focused on dispelling myths and raising awareness about preventive measures, with 100% of individuals reporting prior doubts about the disease, emphasizing the essential nature of the clarification, especially regarding preventive aspects. This study underscores the importance of community involvement, personalized interventions, and ongoing education to effectively combat rabies. By reinforcing public health policies and promoting health education, we can empower communities to take proactive measures in rabies prevention, leading to a reduction in incidence and an improvement in quality of life.
Topics: Animals; Humans; Rabies; Chiroptera; Quality of Life; Zoonoses; Power, Psychological
PubMed: 38276811
DOI: 10.3390/ijerph21010117 -
Viruses Jan 2024Rabies encephalitis has plagued humankind for thousands of years. In developed countries, access to preventive care, both pre-exposure and post-exposure, has... (Review)
Review
Rabies encephalitis has plagued humankind for thousands of years. In developed countries, access to preventive care, both pre-exposure and post-exposure, has significantly reduced the burden of suffering and disease. However, around the world, rabies remains a neglected tropical disease, largely due to uncontrolled dog rabies, and tens of thousands perish each year. Currently, the standard of care for management of rabies encephalitis is palliation. Heroic attempts to treat human rabies patients over the last few decades have yielded glimpses into our understanding of pathophysiology, opening the door to the development of new antiviral therapies and modalities of treatment. Researchers continue to investigate new compounds and approaches to therapy, yet there remain real challenges given the complexity of the disease. We explore and review some of the promising therapies on the horizon in pursuit of a salvage treatment for rabies.
Topics: Humans; Animals; Dogs; Rabies; Zoonoses; Rabies virus; Encephalitis; Rabies Vaccines
PubMed: 38275970
DOI: 10.3390/v16010160 -
PloS One 2024It is not possible to systematically screen the environment for rabies virus (RABV) using current approaches. We sought to determine under what conditions RABV is...
It is not possible to systematically screen the environment for rabies virus (RABV) using current approaches. We sought to determine under what conditions RABV is detectable from feces and other accessible samples from infected wildlife to broaden the number of biological samples that could be used to test for RABV. We employed a recently-developed quantitative RT-PCR assay called the "LN34 panlyssavirus real-time RT-PCR assay", which is highly sensitive and specific for all variants of RABV. We harvested and tested brain tissue, fecal, and/or mouth swab samples from 25 confirmed RABV positive bats of six species. To determine if rabies RNA lasts in feces sufficiently long post-defecation to use it as a surveillance tool, we tested fecal samples from 10 bats at the time of sample collection and after 24 hours of exposure to ambient conditions, with an additional test on six bats out to 72 hours. To assess whether we could pool fecal pellets and still detect a positive, we generated dilutions of known positives at 1:1, 1:10, 1:50, and 1:200. For six individuals for which matched brain, mouth swab, and fecal samples were tested, results were positive for 100%, 67%, and 67%, respectively. For the first time test to 24 hours, 63% of feces that were positive at time 0 were still positive after 24 hours, and 50% of samples at 72 hours were positive across all three replicates. Pooling tests revealed that fecal positives were detected at 1:10 dilution, but not at 1:50 or 1:200. Our preliminary results suggest that fecal samples hold promise for a rapid and non-invasive environmental screening system.
Topics: Humans; Animals; Rabies virus; Rabies; Chiroptera; Body Fluids; Feces; Lepidoptera
PubMed: 38261561
DOI: 10.1371/journal.pone.0294122 -
Vaccines Jan 2024Lyme disease (LD) is the most common tick-borne illness in the United States (U.S.), Europe, and Asia. , a spirochete bacterium transmitted by the tick vector , causes...
Lyme disease (LD) is the most common tick-borne illness in the United States (U.S.), Europe, and Asia. , a spirochete bacterium transmitted by the tick vector , causes LD in the U.S. If untreated, Lyme arthritis, heart block, and meningitis can occur. Given the absence of a human Lyme disease vaccine, we developed a vaccine using the rabies virus (RABV) vaccine vector BNSP333 and an outer surface borrelial protein, BBI39. BBI39 was previously utilized as a recombinant protein vaccine and was protective in challenge experiments; therefore, we decided to utilize this protective antigen in a rabies virus-vectored vaccine against To incorporate BBI39 into the RABV virion, we generated a chimeric BBI39 antigen, BBI39, by fusing BBI39 with the final amino acids of the RABV glycoprotein by molecular cloning and viral recovery with reverse transcription genetics. Here, we have demonstrated that the BBI39 antigen was incorporated into the RABV virion via immunofluorescence and Western blot analysis. Mice vaccinated with our BPL inactivated RABV-BBI39 (BNSP333-BBI39) vaccine induced high amounts of BBI39-specific antibodies, which were maintained long-term, up to eight months post-vaccination. The BBI39 antibodies neutralized in vaccinated mice when challenged with by either syringe injection or infected ticks and they reduced the Lyme disease pathology of arthritis in infected mouse joints. Overall, the RABV-based LD vaccine induced more and longer-term antibodies compared to the recombinant protein vaccine. This resulted in lower borrelial RNA in RABV-based vaccinated mice compared to recombinant protein vaccinated mice. The results of this study indicate the successful use of BBI39 as a vaccine antigen and RABV as a vaccine vector for LD.
PubMed: 38250891
DOI: 10.3390/vaccines12010078 -
Theranostics 2024Neurons in the ventral tegmental area (VTA) are sensitive to stress and their maladaptation have been implicated in the psychiatric disorders such as anxiety and...
Neurons in the ventral tegmental area (VTA) are sensitive to stress and their maladaptation have been implicated in the psychiatric disorders such as anxiety and addiction, . The cellular properties of the VTA neurons in response to different stressors related to different emotional processing remain to be investigated. By combining immediate early gene (IEG)-dependent labeling, rabies virus tracing, ensemble-specific transcriptomic analysis and fiber photometry recording in the VTA of male mice, the spatial distribution, brain-wide connectivity and cellular signaling pathways in the VTA neuronal ensembles in response to morphine (Mor-Ens) or foot shock (Shock-Ens) stimuli were investigated. Optogenetic activation of the Mor-Ens drove approach behavior, whereas chemogenetic activation of the Shock-Ens increased the anxiety level in mice. Mor-Ens were clustered and enriched in the ventral VTA, contained a higher proportion of dopaminergic neurons, received more inputs from the dorsal medial striatum and the medial hypothalamic zone, and exhibited greater axonal arborization in the zona incerta and ventral pallidum. Whereas Shock-Ens were more dispersed, contained a higher proportion of GABAergic neurons, and received more inputs from the ventral pallidum and the lateral hypothalamic area. The downstream targets of the G protein and β-arrestin pathways, PLCβ3 and phosphorylated AKT1, were relatively enriched in the Mor-Ens and Shock-Ens, respectively. Cariprazine, the G-protein-biased agonist for the dopamine D2 receptor, increased the response of Mor-Ens to sucrose water and decreased the anxiety-like behavior during morphine withdrawal, whereas the β-arrestin-biased agonist UNC9994 decreased the response of Shock-Ens to tail suspension. Taken together, these findings reveal the heterogeneous connectivity and signaling pathways of the VTA neurons in response to morphine and foot shock, providing new insights for development of specific interventions for psychiatric disorders caused by various stressors associated with different VTA neuronal functions.
Topics: Humans; Male; Animals; Mice; Ventral Tegmental Area; Dopaminergic Neurons; Signal Transduction; beta-Arrestins; Morphine Derivatives
PubMed: 38250036
DOI: 10.7150/thno.90792 -
Cells Jan 2024Rabies virus (RABV) is a single-stranded negative-sense RNA virus belonging to the family and genus, which is highly neurotropic and can infect almost all warm-blooded... (Review)
Review
Rabies virus (RABV) is a single-stranded negative-sense RNA virus belonging to the family and genus, which is highly neurotropic and can infect almost all warm-blooded animals, including humans. Autophagy and apoptosis are two evolutionarily conserved and genetically regulated processes that maintain cellular and organismal homeostasis, respectively. Autophagy recycles unnecessary or dysfunctional intracellular organelles and molecules in a cell, whereas apoptosis eliminates damaged or unwanted cells in an organism. Studies have shown that RABV can induce both autophagy and apoptosis in target cells. To advance our understanding of pathogenesis of rabies, this paper reviews the molecular mechanisms of autophagy and apoptosis induced by RABV and the effects of the two cellular events on RABV replication.
Topics: Animals; Humans; Rabies virus; Rabies; Apoptosis; Autophagy; Virus Replication
PubMed: 38247875
DOI: 10.3390/cells13020183 -
PloS One 2024Contagious ecthyma is a skin disease, caused by Orf virus, creating great economic threats to livestock farming worldwide. Zoonotic potential of this disease has gained...
Contagious ecthyma is a skin disease, caused by Orf virus, creating great economic threats to livestock farming worldwide. Zoonotic potential of this disease has gained recent attention owing to the re-emergence of disease in several parts of the world. Increased public health concern emphasizes the need for a predictive understanding of the geographic distributional potential of Orf virus. Here, we mapped the current distribution using occurrence records, and estimated the ecological niche in both geographical and environmental spaces. Twenty modeling experiments, resulting from two- and three-partition models, were performed to choose the candidate models that best represent the geographic distributional potential of Orf virus. For all of our models, it was possible to reject the null hypothesis of predictive performance no better than random expectations. However, statistical significance must be accompanied by sufficiently good predictive performance if a model is to be useful. In our case, omission of known distribution of the virus was noticed in all Maxent models, indicating inferior quality of our models. This conclusion was further confirmed by the independent final evaluation, using occurrence records sourced from the Centre for Agriculture and Bioscience International. Minimum volume ellipsoid (MVE) models indicated the broad range of environmental conditions under which Orf virus infections are found. The excluded climatic conditions from MVEs could not be considered as unsuitable owing to the broad distribution of Orf virus. These results suggest two possibilities: that the niche models fail to identify niche limits that constrain the virus, or that the virus has no detectable niche, as it can be found throughout the geographic distributions of its hosts. This potential limitation of component-based pathogen-only ENMs is discussed in detail.
Topics: Sheep; Animals; Orf virus; Poxviridae; Ecosystem; Ecthyma, Contagious; Geography
PubMed: 38236902
DOI: 10.1371/journal.pone.0293312 -
Viruses Dec 2023Australian bat lyssavirus (ABLV) shows similar clinical symptoms as rabies, but there are currently no protein structures available for ABLV proteins. In lyssaviruses,...
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 (NP) 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 NP demonstrated a highly conserved interface in this complex. Because the NP interface is conserved in the lyssaviruses of phylogroup I, it is an attractive therapeutic target for multiple rabies-causing viral species.
Topics: Animals; Lyssavirus; Rabies; Nucleoproteins; Chiroptera; Australia; Phosphoproteins; Rhabdoviridae Infections
PubMed: 38229694
DOI: 10.3390/v16010033 -
Korean Journal of Neurotrauma Dec 2023Few cases of injuries caused by wild boars have been reported in the literature. Here, we present the case of a 64-year-old male patient who was attacked by a wild boar....
Few cases of injuries caused by wild boars have been reported in the literature. Here, we present the case of a 64-year-old male patient who was attacked by a wild boar. The patient had a laceration to the right forehead and a penetrating wound in the area before the right auricle. Computed tomography scan revealed traumatic subarachnoid hemorrhage, subdural hemorrhage, right temporal lobe contusion hemorrhage, pneumocephalus, right zygomatic arch and temporal bone fracture, and right coronal process fracture of the mandible. Prophylactically, 2,000 mg of ceftriaxone and 400 mg of moxifloxacin were intravenously administered every 24 hours. An emergency craniectomy was performed because the skull fracture was an open fracture and control of the increased intracranial pressure was necessary. Inactivated Rabies Virus Vaccine was also administered postoperatively. We concluded that, unlike typical wounds from other traumatic causes, the risk of wound infection is higher. In order to reduce morbidity and mortality due to wild boar attacks, rapid stabilization of the patient's vital signs, prevention of infection with appropriate antibiotics, and surgical intervention at the appropriate time and method are necessary.
PubMed: 38222830
DOI: 10.13004/kjnt.2023.19.e59 -
Nature Neuroscience Feb 2024Rabies-virus-based monosynaptic tracing is a widely used technique for mapping neural circuitry, but its cytotoxicity has confined it primarily to anatomical...
Rabies-virus-based monosynaptic tracing is a widely used technique for mapping neural circuitry, but its cytotoxicity has confined it primarily to anatomical applications. Here we present a second-generation system for labeling direct inputs to targeted neuronal populations with minimal toxicity, using double-deletion-mutant rabies viruses. Viral spread requires expression of both deleted viral genes in trans in postsynaptic source cells. Suppressing this expression with doxycycline following an initial period of viral replication reduces toxicity to postsynaptic cells. Longitudinal two-photon imaging in vivo indicated that over 90% of both presynaptic and source cells survived for the full 12-week course of imaging. Ex vivo whole-cell recordings at 5 weeks postinfection showed that the second-generation system perturbs input and source cells much less than the first-generation system. Finally, two-photon calcium imaging of labeled networks of visual cortex neurons showed that their visual response properties appeared normal for 10 weeks, the longest we followed them.
Topics: Rabies virus; Neurons; Virus Replication
PubMed: 38212587
DOI: 10.1038/s41593-023-01545-8