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PloS One 2023With over 1,400 species worldwide, bats represent the second largest order of mammals after rodents, and are known to host major zoonotic pathogens. Here, we estimate...
With over 1,400 species worldwide, bats represent the second largest order of mammals after rodents, and are known to host major zoonotic pathogens. Here, we estimate the presence of pathogens in autochthonous bat populations. First, we set out to check our samples for PCR amplification efficiency by assessing the occurrence of inhibited PCR reactions from different types of bat samples with amplifying the housekeeping gene β-actin. Second, we investigated the presence of five targeted pathogens in a French bat population using PCR. We targeted viral RNA of Canine distemper virus, Alphacoronavirus, Lyssavirus, Rotavirus and bacterial Leptospira DNA. To do so, we screened for these viruses in bat faecal samples as well as in oropharyngeal swab samples. The presence of Leptospira was assessed in urine, kidney, lung and faecal samples. Results showed a frequency of inhibited reactions ranging from 5 to 60% of samples, varying according to the sample itself and also suspected to vary according to sampling method and the storage buffer solution used, demonstrating the importance of the sampling and storage on the probability of obtaining negative PCR results. For pathogen assessment, rotavirus and alphacoronavirus RNA were detected in Myotis myotis, Myotis daubentonii, Myotis emarginatus and Rhinolophus ferrumequinum bats. Rotaviruses were also detected in Barbastella barbastellus. The presence of alphacoronavirus also varied seasonally, with higher frequencies in late summer and October, suggesting that juveniles potentially play an important role in the dynamics of these viruses. Leptospira DNA was detected in M. myotis and M. daubentonii colonies. The 16S rRNA sequences obtained from Leptospira positive samples showed 100% genetic identity with L. borgpetersenii. Neither canine distemper virus nor lyssavirus RNA were detected in any of the tested samples. This study is the first to show the presence of Leptospira in autochthonous French bats in addition to coronavirus and rotavirus RNA previously reported in European autochthonous bats.
Topics: Animals; Chiroptera; Leptospira; RNA, Ribosomal, 16S; Lyssavirus; France; DNA, Bacterial; Phylogeny
PubMed: 37862301
DOI: 10.1371/journal.pone.0292840 -
Viruses Aug 2023Rabies is a fatal zoonosis that is considered a re-emerging infectious disease. Although rabies remains endemic in canines throughout much of the world, vaccination...
Rabies is a fatal zoonosis that is considered a re-emerging infectious disease. Although rabies remains endemic in canines throughout much of the world, vaccination programs have essentially eliminated dog rabies in the Americas and much of Europe. However, despite the goal of eliminating dog rabies in the European Union by 2020, sporadic cases of dog rabies still occur in Eastern Europe, including Georgia. To assess the genetic diversity of the strains recently circulating in Georgia, we sequenced seventy-eight RABV-positive samples from the brain tissues of rabid dogs and jackals using Illumina short-read sequencing of total RNA shotgun libraries. Seventy-seven RABV genomes were successfully assembled and annotated, with seventy-four of them reaching the coding-complete status. Phylogenetic analyses of the nucleoprotein (N) and attachment glycoprotein (G) genes placed all the assembled genomes into the Cosmopolitan clade, consistent with the Georgian origin of the samples. An amino acid alignment of the G glycoprotein ectodomain identified twelve different sequences for this domain among the samples. Only one of the ectodomain groups contained a residue change in an antigenic site, an R264H change in the G5 antigenic site. Three isolates were cultured, and these were found to be efficiently neutralized by the human monoclonal antibody A6. Overall, our data show that recently circulating RABV isolates from Georgian canines are predominantly closely related phylogroup I viruses of the Cosmopolitan clade. Current human rabies vaccines should offer protection against infection by Georgian canine RABVs. The genomes have been deposited in GenBank (accessions: OQ603609-OQ603685).
Topics: Dogs; Animals; Humans; Rabies virus; Rabies; Phylogeny; Rabies Vaccines; Jackals; Glycoproteins; Genomics
PubMed: 37766204
DOI: 10.3390/v15091797 -
Infection, Genetics and Evolution :... Sep 2023South-East Asia (SEA) and South Asia (SA) are two important geographic regions with the most severe enzootic rabies in the world. In these regions, phylogenetic analysis...
South-East Asia (SEA) and South Asia (SA) are two important geographic regions with the most severe enzootic rabies in the world. In these regions, phylogenetic analysis of rabies virus (RABV) has been conducted only at a country level; the results obtained from different countries are scattered and unequal, with a non-uniform system to name RABV genotypes. Therefore, it is difficult to undertake origin-tracking and compare inter-country RABV evolution and transmission. To avoid the confusion in understanding and to generate a panoramic picture of RABV genetic diversity, distribution, and transmission in SEA and SA, the present study conducted a systematic phylogenetic analysis by combining all sequences representing 2368 RABV strains submitted to GenBank by 14 rabies endemic SEA and SA countries. The results showed that RABVs circulating in two regions were classified into four major clades and many subclades: the Asia clade is circulating only in SEA, the Indian subcontinent, and Arctic-like clades only in SA, while the Cosmopolitan clade has been detected in both regions. The results also showed a wide range of hosts were infected by divergent RABV subclades, with dogs being the major transmission source. However, wildlife rabies was also found to be an important issue with 6 wild carnivore species identified as potential sources of spillover risk for sylvatic rabies to humans, domestic animals, and other wild animals. Current findings indicate that the two regions have separate virus clades circulating thus indicating the absence of cross-transmission between the regions. The study emphasizes the importance of phylogenetic analysis in the regions using uniform genotyping and naming systems for rabies surveillance, to coordinate actions of member countries to eliminate dog-mediated human rabies by 2030.
Topics: Animals; Humans; Dogs; Rabies virus; Rabies; Phylogeny; Asia, Southern; Animals, Wild; Genetic Variation
PubMed: 37353186
DOI: 10.1016/j.meegid.2023.105472 -
PloS One 2023Although Japan has been a rabies-free country for >50 years, a few cases have been reported among people traveling abroad. This study aimed to investigate animal...
BACKGROUND
Although Japan has been a rabies-free country for >50 years, a few cases have been reported among people traveling abroad. This study aimed to investigate animal exposure among Japanese travelers using the Japanese Registry for Infectious Diseases from Abroad (J-RIDA).
METHOD
In this retrospective analysis, we examined Japanese overseas travelers with animal exposure, as included the J-RIDA database, reported from October 1, 2017, to October 31, 2019, with a focus on pre-exposure prophylaxis (PrEP) administration and the animals to which the patients were exposed.
RESULTS
Among the 322 cases included in the analysis, 19 (5.9%) patients received PrEP and 303 did not. The most common purpose of travel was a non-package tour (n = 175, 54.3%). Most trips (n = 213, 66.1%) were to a single country for <2 weeks. Most patients (n = 286, 87.9%) traveled to countries with a rabies risk. The majority of patients with and without PrEP were injured in rabies-risk countries [n = 270 (89.1%) for non-PrEP and n = 16 (84.2%) for PrEP]. Animals associated with injuries included dogs (55.0%), cats (25.5%), and monkeys (15.5%). Most patients were classified as World Health Organization Category II/III for contact with suspected rabid animals (39.5% and 44.1% for categories II and III, respectively) and had exposure within 5 days of travel. Southeast Asia (n = 180, 55.9%) was the most common region in which travelers were exposed to animals.
CONCLUSIONS
Japanese overseas travelers had contact with animals that could possibly transmit the rabies virus, even on short trips. Promoting pre-travel consultation and increasing awareness of the potential for rabies exposure are important for prevention of rabies among Japanese international travelers.
Topics: Animals; Dogs; Humans; East Asian People; Rabies; Rabies virus; Retrospective Studies; Travel
PubMed: 37595010
DOI: 10.1371/journal.pone.0287838 -
Frontiers in Veterinary Science 2023Viruses of the genus are classified into several genotypes (GT1 to GT7), of which only GT1 (classic rabies virus-RABV) has a cosmopolitan distribution and circulates in...
Viruses of the genus are classified into several genotypes (GT1 to GT7), of which only GT1 (classic rabies virus-RABV) has a cosmopolitan distribution and circulates in Brazil. GT1 is subdivided into several antigenic variants (AgV) maintained in independent cycles with a narrow host range and distinct geographic distributions, namely, AgV1 and AgV2 found in dogs, AgV3 in the vampire bats , and AgV4 and AgV6 in bats non-hematophagous and , a common variant of marmoset (), and crab-eating fox (). In this study, we performed phylogenetic analysis to identify at the antigenic variant level; six RABV genomes derived from the Rabies Surveillance in the north and northeast regions of Brazil. The analysis resulted in the formation of 11 monophyletic clusters, each corresponding to a particular variant, with high bootstrap support values. The samples were positioned inside the AgV3, AgV6, and variant clades. This is the first report of the AgV6 variant found in northern Brazil, which provides valuable information for rabies surveillance in the country. The possibility of viral spillover has been much debated, as it deals with the risk of shifting transmission from a primary to a secondary host. However, more genomic surveillance studies should be performed, with a greater number and diversity of samples to better understand the transmission dynamics of each variant to detect changes in its geographic distribution and spillover events.
PubMed: 37841469
DOI: 10.3389/fvets.2023.1257558 -
Genes Jul 2023Rabies remains a great threat to public health worldwide. So far, the mechanism of rabies virus (RABV) infection is not fully understood, and there is no effective...
Rabies remains a great threat to public health worldwide. So far, the mechanism of rabies virus (RABV) infection is not fully understood, and there is no effective treatment for rabies. Identifying more host restriction factors of RABV will spur the development of novel therapeutic interventions against rabies. Accumulating studies suggest that tripartite motif-containing (TRIM) proteins have great effects on virus replication. TRIMs control the antiviral responses through either direct interaction with viral proteins or indirect regulation of innate immune signaling molecules in the host. The role of TRIM25 in rabies virus (RABV) infection is poorly understood. Using next-generation sequencing, we found that TRIM25 is upregulated during HEP-Flury infection. Knockdown of TRIM25 enhances HEP-Flury production, while overexpression of TRIM25 suppresses HEP-Flury replication. Knockdown of interferon α and interferon β weakens the anti-RABV response induced by TRIM25 overexpression, and potentiates RABV production. Furthermore, we found that TRIM25 regulates type-I interferon response by targeting retinoic acid-inducible gene I (RIG-I) during HEP-Flury infection. Knockdown of RIG-I weakens the anti-HEP-Flury response induced by TRIM25 overexpression, indicating that TRIM25 regulates RABV production via the RIG-I-IFN axis. In addition, we observed that TRIM25 does not directly interact with HEP-Flury structural proteins, suggesting that TRIM25 regulates HEP-Flury production indirectly. Taken together, our work identifies TRIM25 as a new host factor involved in HEP-Flury infection, which may be a potential target for the development of antiviral drugs against RABV.
Topics: Humans; Rabies virus; Interferon Type I; Rabies; Antiviral Agents; Interferon-beta; Tripartite Motif Proteins; Transcription Factors; Ubiquitin-Protein Ligases
PubMed: 37628607
DOI: 10.3390/genes14081555 -
Vaccines Aug 2023Rabies encephalitis is a fatal zoonotic viral disease caused by the neurotropic rabies virus. It remains a major public health concern as it causes almost 100% fatality...
Rabies encephalitis is a fatal zoonotic viral disease caused by the neurotropic rabies virus. It remains a major public health concern as it causes almost 100% fatality and has no effective medication after the onset of the disease. However, this illness is preventable with the timely administration of effective post-exposure prophylaxis (PEP) consisting of the rabies vaccine and passive immune globulins (HRIG and ERIG). Recently, conventional PEP has been shown to have many limitations, resulting in little support for these expensive and heterologous globulins. Monoclonal antibody (mAb) production via recombinant technology in animal and human cell cultures, as well as a plant-based platform, was introduced to overcome the costly and high-tech constraints of former preparations. We used transient expression technology to produce two mAbs against the rabies virus in and compared their viral neutralizing activity in vitro and in vivo. The expression levels of selective mAbs E559 and 62-71-3 in plants were estimated to be 17.3 mg/kg and 28.6 mg/kg in fresh weight, respectively. The plant-produced mAbs effectively neutralized the challenge virus CVS-11 strain in a cell-based RFFIT. In addition, the combination of these two mAbs in a cocktail protected hamsters from rabies virus infection more effectively than standard HRIG and ERIG. This study suggests that the plant-produced rabies antibody cocktail has promising potential as an alternative biological to polyclonal RIG in rabies PEP.
PubMed: 37631945
DOI: 10.3390/vaccines11081377 -
Journal of Virology Jul 2023Mounting evidence suggests that gut microbial composition and its metabolites, including short-chain fatty acids (SCFAs), have beneficial effects in regulating host...
Short-Chain Fatty Acids Alleviate Vancomycin-Caused Humoral Immunity Attenuation in Rabies-Vaccinated Mice by Promoting the Generation of Plasma Cells via Akt-mTOR Pathway.
Mounting evidence suggests that gut microbial composition and its metabolites, including short-chain fatty acids (SCFAs), have beneficial effects in regulating host immunogenicity to vaccines. However, it remains unknown whether and how SCFAs improve the immunogenicity of the rabies vaccine. In this study, we investigated the effect of SCFAs on the immune response to rabies vaccine in vancomycin (Vanco)-treated mice and found that oral gavage with butyrate-producing bacteria () and butyrate supplementation elevated RABV-specific IgM, IgG, and virus-neutralizing antibodies (VNAs) in Vanco-treated mice. Supplementation with butyrate expanded antigen-specific CD4 T cells and IFN-γ-secreting cells, augmented germinal center (GC) B cell recruitment, promoted plasma cells (PCs) and RABV-specific antibody-secreting cells (ASCs) generation in Vanco-treated mice. Mechanistically, butyrate enhanced mitochondrial function and activated the Akt-mTOR pathway in primary B cells isolated from Vanco-treated mice, ultimately promoting B lymphocyte-induced maturation protein-1 (Blimp-1) expression and CD138 PCs generation. These results highlight the important role of butyrate in alleviating Vanco-caused humoral immunity attenuation in rabies-vaccinated mice and maintaining host immune homeostasis. The gut microbiome plays many crucial roles in the maintenance of immune homeostasis. Alteration of the gut microbiome and metabolites has been shown to impact vaccine efficacy. SCFAs can act as an energy source for B-cells, thereby promoting both mucosal and systemic immunity in the host by inhibiting HDACs and activation of GPR receptors. This study investigates the impact of orally administered butyrate, an SCFA, on the immunogenicity of rabies vaccines in Vanco-treated mice. The results showed that butyrate ameliorated humoral immunity by facilitating the generation of plasma cells via the Akt-mTOR in Vanco-treated mice. These findings unveil the impact of SCFAs on the immune response of the rabies vaccine and confirm the crucial role of butyrate in regulating immunogenicity to rabies vaccines in antibiotic-treated mice. This study provides a fresh insight into the relationship of microbial metabolites and rabies vaccination.
Topics: Mice; Animals; Rabies; Rabies Vaccines; Plasma Cells; Immunity, Humoral; Vancomycin; Proto-Oncogene Proteins c-akt; Antibodies, Viral; TOR Serine-Threonine Kinases; Fatty Acids, Volatile; Butyrates
PubMed: 37338411
DOI: 10.1128/jvi.00656-23 -
International Journal of Molecular... May 2024Rabies virus (RABV) is a neurotropic virus that causes fatal neurological disease, raising serious public health issues and attracting extensive attention in society. To...
Rabies virus (RABV) is a neurotropic virus that causes fatal neurological disease, raising serious public health issues and attracting extensive attention in society. To elucidate the molecular mechanism of RABV-induced neuronal damage, we used hematoxylin-eosin staining, transmission electron microscopy, transcriptomics analysis, and immune response factor testing to investigate RABV-infected neurons. We successfully isolated the neurons from murine brains. The specificity of the isolated neurons was identified by a monoclonal antibody, and the viability of the neurons was 83.53-95.0%. We confirmed that RABV infection induced serious damage to the neurons according to histochemistry and transmission electron microscope (TEM) scanning. In addition, the transcriptomics analysis suggested that multiple genes related to the pyroptosis pathway were significantly upregulated, including (), , , and , as well as the chemokine genes , , , , , , and . We next verified this finding in the brains of mice infected with the rRC-HL, GX074, and challenge virus standard strain-24 (CVS-24) strains of RABV. Importantly, we found that the expression level of the Gsdmd protein was significantly upregulated in the neurons infected with different RABV strains and ranged from 691.1 to 5764.96 pg/mL, while the basal level of mock-infected neurons was less than 100 pg/mL. Taken together, our findings suggest that Gsdmd-induced pyroptosis is involved in the neuron damage caused by RABV infection.
Topics: Animals; Pyroptosis; Neurons; Rabies virus; Rabies; Mice; Phosphate-Binding Proteins; Intracellular Signaling Peptides and Proteins; Brain; Gasdermins
PubMed: 38891803
DOI: 10.3390/ijms25115616 -
Pathogens (Basel, Switzerland) Oct 2023Rabies is one of the most significant public and veterinary health problems, causing approximately 59,000 human deaths annually in the developing countries of Asia and...
Molecular Characterization of Lyssaviruses Originating from Domestic and Wild Cats Provides an Insight on the Diversity of Lyssaviruses and a Risk of Rabies Transmission to Other Susceptible Mammals and Humans in South Africa.
Rabies is one of the most significant public and veterinary health problems, causing approximately 59,000 human deaths annually in the developing countries of Asia and Africa. The aetiologic agent, a viral species of the genus, is highly neurotropic and has a wide host range, including terrestrial mammals and several species. The (MOKV) was first isolated in the late 1960s from organ pools of shrews () in the Mokola forest (Nigeria). To date, at least 30 MOKV isolations have been confirmed, all exclusively from Africa, with 73% from southern Africa. There is limited knowledge about the epidemiology of MOKV, and the reservoir host species is unknown. Here, we report on the molecular characterization of rabies viruses originating from both domestic and African wild cats. A partial region of the lyssavirus genome, encoding the nucleoprotein, was amplified and sequenced. Nucleotide sequence analysis demonstrated that 98% of cats were infected with both the canid and mongoose rabies virus variants, as well as a rare lyssavirus, , from a domestic cat from Eswatini. Furthermore, the nucleotide sequence divergence between the recently identified MOKV isolate and the historical isolates ranged from 6.8% to 8.3%. This study further highlights the association between the potential host species of and the domestic cat as an incidental host, and the important role cats may play in rabies transmission dynamics in the country. Therefore, continuous vaccination of domestic cats against rabies is crucial, even after the elimination of dog-mediated rabies, as spillover related to sylvatic rabies cycles is likely to occur.
PubMed: 37887728
DOI: 10.3390/pathogens12101212