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Biology Letters Sep 2022Rabies virus (RABV) transmitted by the common vampire bat () poses a threat to agricultural development and public health throughout the Neotropics. The ecology and... (Review)
Review
Rabies virus (RABV) transmitted by the common vampire bat () poses a threat to agricultural development and public health throughout the Neotropics. The ecology and evolution of rabies host-pathogen dynamics are influenced by two infection-induced behavioural changes. RABV-infected hosts often exhibit increased aggression which facilitates transmission, and rabies also leads to reduced activity and paralysis prior to death. Although several studies document rabies-induced behavioural changes in rodents and other dead-end hosts, surprisingly few studies have measured these changes in vampire bats, the key natural reservoir throughout Latin America. Taking advantage of an experiment designed to test an oral rabies vaccine in captive male vampire bats, we quantify for the first time, to our knowledge, how rabies affects allogrooming and aggressive behaviours in this species. Compared to non-rabid vampire bats, rabid individuals reduced their allogrooming prior to death, but we did not detect increases in aggression among bats. To put our results in context, we review what is known and what remains unclear about behavioural changes of rabid vampire bats (resumen en español, electronic supplementary material, S1).
Topics: Animals; Chiroptera; Male; Rabies; Rabies Vaccines; Rabies virus
PubMed: 36069068
DOI: 10.1098/rsbl.2022.0298 -
Pathogens (Basel, Switzerland) Mar 2021Lyme borreliosis (LB) is the most common tick-borne disease in Serbia and other European countries. Rabies is a fatal zoonosis distributed worldwide and is caused by the...
Lyme borreliosis (LB) is the most common tick-borne disease in Serbia and other European countries. Rabies is a fatal zoonosis distributed worldwide and is caused by the rabies virus. Professionals at risk of rabies-including veterinarians, hunters, communal service workers, and forestry workers-overlap with some professions at a higher risk of exposure to tick bites and tick-borne pathogen infections. We hypothesized that individuals identified by the public health system as at risk of rabies virus infection, and consequently vaccinated against rabies virus, also share a higher likelihood of exposure. To test our hypothesis, a case-control study was carried out during 2019 in Serbia to determine the seroprevalence of anti- antibodies in two case groups (individuals at risk and vaccinated against rabies virus) and a control group (individuals without risk of rabies). Individuals vaccinated against rabies following either "pre-exposure protocol" (PrEP, = 58) or "post-exposure protocol" (PEP, = 42) were considered as rabies risk groups and healthy blood donors ( = 30) as the control group. The results showed higher seroprevalence in PrEP (17.2%; 10/58) and PEP (19.0%; 8/42) groups compared with the control group (6.67%; 2/30). Furthermore, odds ratio (OR) analysis showed that risk of rabies (in either the PrEP (OR = 2.91) or PEP (OR = 3.29) groups) is associated with increased odds of being seropositive to . However, the difference in seroprevalence between groups was not statistically significant (Chi-square (χ²) test > 0.05). The shared odds of LB and rabies exposure found in this study suggest that, in countries where both diseases occur, the common citizen can be at risk of both diseases when in a risky habitat. These findings are important to guide physicians in targeting high-risk groups, and diagnose LB, and to guide decision-makers in targeting control and prevention measures for both infections in risk areas.
PubMed: 33800537
DOI: 10.3390/pathogens10040399 -
Infectious Medicine Dec 2022Rabies is a zoonotic infectious disease with a high fatality rate. It is caused by a virus in the genus and is a global public health threat. The rabies virus invades... (Review)
Review
Rabies is a zoonotic infectious disease with a high fatality rate. It is caused by a virus in the genus and is a global public health threat. The rabies virus invades and infects cells mainly via a glycoprotein, which may involve multiple receptors. Neutralizing antibodies against the rabies virus function by blocking the binding of the glycoprotein to a receptor or preventing the membrane fusion process. Vaccination combined with anti-rabies virus neutralizing antibodies is essential for postexposure prophylaxis for category III exposure to the rabies virus. In this review, we discussed the neutralizing epitopes of the rabies virus and the neutralization mechanism of monoclonal antibodies. The neutralizing antibodies that have been commercialized or are under development are also summarized. Our review would provide a basis for the further development of safe and effective broad-spectrum neutralizing antibodies to replace the rabies virus immunoglobulin in rabies post-exposure prophylaxis.
PubMed: 38075404
DOI: 10.1016/j.imj.2022.09.003 -
Scientific Reports Jun 2023Raccoons (Procyon lotor) are routinely translocated both legally and illegally to mitigate conflicts with humans, which has contributed to the spread of rabies virus...
Raccoons (Procyon lotor) are routinely translocated both legally and illegally to mitigate conflicts with humans, which has contributed to the spread of rabies virus across eastern North America. The movement behavior of translocated raccoons has important ramifications for disease transmission yet remains understudied and poorly quantified. To examine the spatial ecology of raccoons following experimental translocation, we performed reciprocal 16 km-distance translocations of 30 raccoons between habitats of high and low raccoon density (bottomland hardwood and upland pine, respectively) across the Savannah River Site (SRS) in Aiken, South Carolina, USA (2018-2019). Translocation influenced patterns of raccoon space use, with translocated animals exhibiting a 13-fold increase in 95% utilization distributions (UDs) post- compared to pre-translocation (mean 95% UD 35.8 ± 36.1 km vs 1.96 ± 1.17 km). Raccoons originating from upland pine habitats consistently had greater space use and larger nightly movement distances post-translocation compared to raccoons moved from bottomland hardwood habitats, whereas these differences were generally not observed prior to translocation. Estimated home ranges of male raccoons were twice the area as estimated for female raccoons, on average, and this pattern was not affected by translocation. After a transient period lasting on average 36.5 days (SD = 30.0, range = 3.25-92.8), raccoons often resumed pre-experiment movement behavior, with 95% UD sizes not different from those prior to translocation (mean = 2.27 ± 1.63km). Most animals established new home ranges after translocation, whereas three raccoons moved > 16 km from their release point back to the original capture location. Four animals crossed a 100-m wide river within the SRS post-translocation, but this behavior was not documented among collared raccoons prior to translocation. Large increases in space use combined with the crossing of geographic barriers such as rivers may lead to elevated contact rates with conspecifics, which can heighten disease transmission risks following translocation. These results provide additional insights regarding the potential impacts of raccoon translocation towards population level risks of rabies outbreaks and underscore the need to discourage mesocarnivore translocations to prevent further spread of wildlife rabies.
Topics: Humans; Animals; Male; Female; Raccoons; Rabies; Animals, Wild; Rabies virus; Disease Outbreaks; Rabies Vaccines
PubMed: 37369730
DOI: 10.1038/s41598-023-37323-6 -
Viruses Apr 2022Rabies is an ancient lethal scourge that has plagued humankind for centuries [...].
Rabies is an ancient lethal scourge that has plagued humankind for centuries [...].
Topics: Humans; Rabies; Rabies virus
PubMed: 35632587
DOI: 10.3390/v14050845 -
BioRxiv : the Preprint Server For... Nov 2023Mapping the connectivity of diverse neuronal types provides the foundation for understanding the structure and function of neural circuits. High-throughput and low-cost...
Mapping the connectivity of diverse neuronal types provides the foundation for understanding the structure and function of neural circuits. High-throughput and low-cost neuroanatomical techniques based on RNA barcode sequencing have the potential to map circuits at cellular resolution and a brain-wide scale, but existing Sindbis virus-based techniques can only map long-range projections using anterograde tracing approaches. Rabies virus can complement anterograde tracing approaches by enabling either retrograde labeling of projection neurons or monosynaptic tracing of direct inputs to genetically targeted postsynaptic neurons. However, barcoded rabies virus has so far been only used to map non-neuronal cellular interactions and synaptic connectivity of cultured neurons. Here we combine barcoded rabies virus with single-cell and sequencing to perform retrograde labeling and transsynaptic labeling in the mouse brain. We sequenced 96 retrogradely labeled cells and 295 transsynaptically labeled cells using single-cell RNA-seq, and 4,130 retrogradely labeled cells and 2,914 transsynaptically labeled cells . We found that the transcriptomic identities of rabies virus-infected cells can be robustly identified using both single-cell RNA-seq and sequencing. By associating gene expression with connectivity inferred from barcode sequencing, we distinguished long-range projecting cortical cell types from multiple cortical areas and identified cell types with converging or diverging synaptic connectivity. Combining sequencing with barcoded rabies virus complements existing sequencing-based neuroanatomical techniques and provides a potential path for mapping synaptic connectivity of neuronal types at scale.
PubMed: 36993334
DOI: 10.1101/2023.03.16.532873 -
Frontiers in Immunology 2021Lyssaviruses cause the disease rabies, which is a fatal encephalitic disease resulting in approximately 59,000 human deaths annually. The prototype species, rabies... (Review)
Review
Lyssaviruses cause the disease rabies, which is a fatal encephalitic disease resulting in approximately 59,000 human deaths annually. The prototype species, rabies lyssavirus, is the most prevalent of all lyssaviruses and poses the greatest public health threat. In Africa, six confirmed and one putative species of lyssavirus have been identified. Rabies lyssavirus remains endemic throughout mainland Africa, where the domestic dog is the primary reservoir - resulting in the highest per capita death rate from rabies globally. Rabies is typically transmitted through the injection of virus-laden saliva through a bite or scratch from an infected animal. Due to the inhibition of specific immune responses by multifunctional viral proteins, the virus usually replicates at low levels in the muscle tissue and subsequently enters the peripheral nervous system at the neuromuscular junction. Pathogenic rabies lyssavirus strains inhibit innate immune signaling and induce cellular apoptosis as the virus progresses to the central nervous system and brain using viral protein facilitated retrograde axonal transport. Rabies manifests in two different forms - the encephalitic and the paralytic form - with differing clinical manifestations and survival times. Disease symptoms are thought to be due mitochondrial dysfunction, rather than neuronal apoptosis. While much is known about rabies, there remain many gaps in knowledge about the neuropathology of the disease. It should be emphasized however, that rabies is vaccine preventable and dog-mediated human rabies has been eliminated in various countries. The global elimination of dog-mediated human rabies in the foreseeable future is therefore an entirely feasible goal.
Topics: Africa; Animals; Dogs; Encephalitis, Viral; Endemic Diseases; Humans; Immunity, Innate; Rabies; Rabies virus; Saliva; Viral Zoonoses; Virus Replication
PubMed: 34925368
DOI: 10.3389/fimmu.2021.786953 -
Proceedings of the National Academy of... May 2022Cortical circuit tracing using modified rabies virus can identify input neurons making direct monosynaptic connections onto neurons of interest. However, challenges...
Cortical circuit tracing using modified rabies virus can identify input neurons making direct monosynaptic connections onto neurons of interest. However, challenges remain in our ability to establish the cell type identity of rabies-labeled input neurons. While transcriptomics may offer an avenue to characterize inputs, the extent of rabies-induced transcriptional changes in distinct neuronal cell types remains unclear, and whether these changes preclude characterization of rabies-infected neurons according to established transcriptomic cell types is unknown. We used single-nucleus RNA sequencing to survey the gene expression profiles of rabies-infected neurons and assessed their correspondence with established transcriptomic cell types. We demonstrated that when using transcriptome-wide RNA profiles, rabies-infected cortical neurons can be transcriptomically characterized despite global and cell-type-specific rabies-induced transcriptional changes. Notably, we found differential modulation of neuronal marker gene expression, suggesting that caution should be taken when attempting to characterize rabies-infected cells with single genes or small gene sets.
Topics: DNA Fingerprinting; Humans; Neurons; Rabies; Rabies virus; Sequence Analysis, RNA; Transcription, Genetic; Transcriptome
PubMed: 35609197
DOI: 10.1073/pnas.2203677119 -
EMBO Molecular Medicine Oct 2023Infections with rabies virus (RABV) and related lyssaviruses are uniformly fatal once virus accesses the central nervous system (CNS) and causes disease signs. Current...
Infections with rabies virus (RABV) and related lyssaviruses are uniformly fatal once virus accesses the central nervous system (CNS) and causes disease signs. Current immunotherapies are thus focused on the early, pre-symptomatic stage of disease, with the goal of peripheral neutralization of virus to prevent CNS infection. Here, we evaluated the therapeutic efficacy of F11, an anti-lyssavirus human monoclonal antibody (mAb), on established lyssavirus infections. We show that a single dose of F11 limits viral load in the brain and reverses disease signs following infection with a lethal dose of lyssavirus, even when administered after initiation of robust virus replication in the CNS. Importantly, we found that F11-dependent neutralization is not sufficient to protect animals from mortality, and a CD4 T cell-dependent adaptive immune response is required for successful control of infection. F11 significantly changes the spectrum of leukocyte populations in the brain, and the FcRγ-binding function of F11 contributes to therapeutic efficacy. Thus, mAb therapy can drive potent neutralization-independent T cell-mediated effects, even against an established CNS infection by a lethal neurotropic virus.
Topics: Animals; Humans; Lyssavirus; Rhabdoviridae Infections; CD4-Positive T-Lymphocytes; Rabies virus; Immunotherapy; Central Nervous System Infections; Antibodies, Monoclonal; Rabies; Chiroptera
PubMed: 37767784
DOI: 10.15252/emmm.202216394 -
Viruses May 2021If the goal of eliminating dog-mediated human rabies by 2030 is to be achieved, effective mass dog vaccination needs to be complemented by effective prophylaxis for... (Review)
Review
If the goal of eliminating dog-mediated human rabies by 2030 is to be achieved, effective mass dog vaccination needs to be complemented by effective prophylaxis for individuals exposed to rabies. Aptamers and short-interfering RNAs (siRNAs) have been successful in therapeutics, but few studies have investigated their potential as rabies therapeutics. In this study, siRNAs and aptamers-using a novel selection method-were developed and tested against rabies virus (RABV) in a post-infection (p.i.) scenario. Multiple means of delivery were tested for siRNAs, including the use of Lipofectamine and conjugation with the developed aptamers. One siRNA (N53) resulted in an 80.13% reduction in viral RNA, while aptamer UPRET 2.03 demonstrated a 61.3% reduction when used alone at 2 h p.i. At 24 h p.i., chimera UPRET 2.03-N8 (aptamer-siRNA) resulted in a 36.5% inhibition of viral replication. To our knowledge, this is the first study using siRNAs or aptamers that (1) demonstrated significant inhibition of RABV using an aptamer, (2) tested Lipofectamine RNAi-Max as a means for delivery, and (3) produced significant RABV inhibition at 24 h p.i. This study serves as a proof-of-concept to potentially use aptamers and siRNAs as rabies immunoglobulin (RIG) replacements or therapeutic options for RABV and provides strong evidence towards their further investigation.
Topics: Animals; Aptamers, Nucleotide; Cells, Cultured; Clinical Trials as Topic; Disease Management; Disease Models, Animal; Genetic Therapy; Humans; Premedication; RNA Interference; RNA, Small Interfering; Rabies; Rabies virus; SELEX Aptamer Technique; Virus Replication
PubMed: 34064911
DOI: 10.3390/v13050881