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Nature Reviews. Microbiology Apr 2018Rabies is a lethal zoonotic disease that is caused by lyssaviruses, most often rabies virus. Despite control efforts, sporadic outbreaks in wildlife populations are... (Review)
Review
Rabies is a lethal zoonotic disease that is caused by lyssaviruses, most often rabies virus. Despite control efforts, sporadic outbreaks in wildlife populations are largely unpredictable, underscoring our incomplete knowledge of what governs viral transmission and spread in reservoir hosts. Furthermore, the evolutionary history of rabies virus and related lyssaviruses remains largely unclear. Robust surveillance efforts combined with diagnostics and disease modelling are now providing insights into the epidemiology and evolution of rabies virus. The immune status of the host, the nature of exposure and strain differences all clearly influence infection and transmission dynamics. In this Review, we focus on rabies virus infections in the wildlife and synthesize current knowledge in the rapidly advancing fields of rabies virus epidemiology and evolution, and advocate for multidisciplinary approaches to advance our understanding of this disease.
Topics: Animals; Evolution, Molecular; Host Specificity; Humans; Population Surveillance; Rabies; Rabies virus; Zoonoses
PubMed: 29479072
DOI: 10.1038/nrmicro.2018.11 -
Revue Scientifique Et Technique... Aug 2018Once clinical disease is manifest, the rabies virus is one of the few pathogens known to science with a near 100% fatality rate and, as such, this zoonotic pathogen has...
Once clinical disease is manifest, the rabies virus is one of the few pathogens known to science with a near 100% fatality rate and, as such, this zoonotic pathogen has shaped both humanity and the history of science. However, today rabies is still considered to be a neglected tropical disease, despite the fact that it causes more than 59,000 human deaths each year. Although effective vaccines are available to combat the disease, the underlying mechanisms of its pathogenicity and immunology remain poorly defined. In this paper, the existing knowledge of the pathogenesis and immunological response to the rabies virus in infected hosts is described.
Topics: Animals; Gene Expression Regulation, Viral; Humans; Rabies; Rabies virus
PubMed: 30747145
DOI: 10.20506/rst.37.2.2805 -
Annual Review of Virology Nov 2015The cultural impact of rabies, the fatal neurological disease caused by infection with rabies virus, registers throughout recorded history. Although rabies has been the... (Review)
Review
The cultural impact of rabies, the fatal neurological disease caused by infection with rabies virus, registers throughout recorded history. Although rabies has been the subject of large-scale public health interventions, chiefly through vaccination efforts, the disease continues to take the lives of about 40,000-70,000 people per year, roughly 40% of whom are children. Most of these deaths occur in resource-poor countries, where lack of infrastructure prevents timely reporting and postexposure prophylaxis and the ubiquity of domestic and wild animal hosts makes eradication unlikely. Moreover, although the disease is rarer than other human infections such as influenza, the prognosis following a bite from a rabid animal is poor: There is currently no effective treatment that will save the life of a symptomatic rabies patient. This review focuses on the major unanswered research questions related to rabies virus pathogenesis, especially those connecting the disease progression of rabies with the complex dysfunction caused by the virus in infected cells. The recent applications of cutting-edge research strategies to this question are described in detail.
Topics: Animals; Humans; Knowledge; Rabies; Rabies virus; Virulence
PubMed: 26958924
DOI: 10.1146/annurev-virology-100114-055157 -
Iranian Biomedical Journal Jul 2021Viruses are obligatory intracellular parasites that use cell proteins to take the control of the cell functions in order to accomplish their life cycle. Studying the... (Review)
Review
Viruses are obligatory intracellular parasites that use cell proteins to take the control of the cell functions in order to accomplish their life cycle. Studying the viral-host interactions would increase our knowledge of the viral biology and mechanisms of pathogenesis. Studies on pathogenesis mechanisms of lyssaviruses, which are the causative agents of rabies, have revealed some important host protein partners for viral proteins, especially for most studied species, i.e. Rabies virus. In this review article, the key physical lyssavirus-host protein interactions, their contributions to rabies infection, and their exploitation are discussed to improve the knowledge about rabies pathogenesis.
Topics: Animals; Host Microbial Interactions; Humans; Lyssavirus; Phagocytosis; Protein Binding; Rabies; Rabies virus
PubMed: 34217155
DOI: 10.52547/ibj.25.4.226 -
Revue Scientifique Et Technique... Aug 2018Bats (order Chiroptera) are the principal reservoir host for 14 of the 16 officially recognised lyssavirus species. Rabies virus is the only lyssavirus that is well...
Bats (order Chiroptera) are the principal reservoir host for 14 of the 16 officially recognised lyssavirus species. Rabies virus is the only lyssavirus that is well established in terrestrial carnivores (worldwide), as well as bats (but only in the Americas). The other bat lyssaviruses occur only outside the Americas. They have a distinct geographical distribution and association with specific bat species, with limited cross-species transmission to other animals and humans, resulting in deadend infections. The nucleoprotein gene is well conserved between all lyssavirus species. Therefore, gold-standard diagnostic techniques detect all lyssaviruses but do not discriminate between viral species. Lyssaviruses are divided into at least three phylogroups, based on their immunogenic and phylogenic properties. Owing to the diversity of glycoproteins among phylogroups, rabies vaccines and immunoglobulins only provide protection against phylogroup I, excluding several of the bat lyssaviruses. Africa hosts a high diversity of lyssaviruses, leading to the hypothesis that this region was the site of emergence; however, this has been challenged by more recent phylogenetic analysis, suggesting a Palearctic origin. Serological evidence indicates a more widespread and even higher diversity of lyssaviruses in bats, suggesting that the incidence of known lyssaviruses is underestimated and several new lyssavirus species are yet to be discovered. Most bats are, however, not able to transmit the virus and therefore pose a low risk to human and animal populations.
Topics: Animal Distribution; Animals; Chiroptera; Genetic Variation; Lyssavirus; Phylogeny
PubMed: 30747140
DOI: 10.20506/rst.37.2.2809 -
Viruses Apr 2021European bat lyssavirus type 1 (EBLV-1) is the causative agent for almost all reported rabies cases found in European bats. In recent years, increasing numbers of...
Full-Genome Sequences and Phylogenetic Analysis of Archived Danish European Bat Lyssavirus 1 (EBLV-1) Emphasize a Higher Genetic Resolution and Spatial Segregation for Sublineage 1a.
European bat lyssavirus type 1 (EBLV-1) is the causative agent for almost all reported rabies cases found in European bats. In recent years, increasing numbers of available EBLV-1 full genomes and their phylogenetic analyses helped to further elucidate the distribution and genetic characteristics of EBLV-1 and its two subtypes, namely EBLV-1a and EBLV-1b. Nonetheless, the absence of full-genome sequences from regions with known detections of EBLV-1 still limit the understanding of the phylogeographic relations between viruses from different European regions. In this study, a set of 21 archived Danish EBLV-1 samples from the years 1985 to 2009 was processed for the acquisition of full-genome sequences using a high-throughput sequencing approach. Subsequent phylogenetic analysis encompassing all available EBLV-1 full genomes from databases revealed the Danish sequences belong to the EBLV-1a subtype and further highlighted the distinct, close phylogenetic relationship of Danish, Dutch and German isolates in this region. In addition, the formation of five putative groups nearly exclusively formed by Danish isolates and the overall increased resolution of the EBLV-1a branch indicate a higher genetic diversity and spatial segregation for this sublineage than was previously known. These results emphasize the importance of phylogenetic analyses of full-genome sequences of lyssaviruses for genetic geography.
Topics: Animals; Archives; Chiroptera; Chromosome Mapping; Chromosome Segregation; Denmark; Genome, Viral; High-Throughput Nucleotide Sequencing; Lyssavirus; Phylogeny; Rabies; Whole Genome Sequencing
PubMed: 33917139
DOI: 10.3390/v13040634 -
Nature Communications Jun 2023Licensed rabies virus vaccines based on whole inactivated virus are effective in humans. However, there is a lack of detailed investigations of the elicited immune...
Licensed rabies virus vaccines based on whole inactivated virus are effective in humans. However, there is a lack of detailed investigations of the elicited immune response, and whether responses can be improved using novel vaccine platforms. Here we show that two doses of a lipid nanoparticle-formulated unmodified mRNA vaccine encoding the rabies virus glycoprotein (RABV-G) induces higher levels of RABV-G specific plasmablasts and T cells in blood, and plasma cells in the bone marrow compared to two doses of Rabipur in non-human primates. The mRNA vaccine also generates higher RABV-G binding and neutralizing antibody titers than Rabipur, while the degree of somatic hypermutation and clonal diversity of the response are similar for the two vaccines. The higher overall antibody titers induced by the mRNA vaccine translates into improved cross-neutralization of related lyssavirus strains, suggesting that this platform has potential for the development of a broadly protective vaccine against these viruses.
Topics: Animals; Humans; Rabies; Rabies Vaccines; Broadly Neutralizing Antibodies; RNA, Messenger; Antibodies, Viral; Rabies virus; Glycoproteins
PubMed: 37349310
DOI: 10.1038/s41467-023-39421-5 -
Microbes and Infection Jan 2018
Topics: Animals; Cells, Cultured; Glycoproteins; Humans; Lyssavirus; Neurons; Rabies; Viral Proteins; Virulence
PubMed: 28986306
DOI: 10.1016/j.micinf.2017.09.012 -
Medecine Sciences : M/S Jan 2013Rabies virus, a neurotropic lyssavirus responsible for unavoidable fatal encephalitis, is transmitted by saliva of infected animals through bite, scratch or licking of...
Rabies virus, a neurotropic lyssavirus responsible for unavoidable fatal encephalitis, is transmitted by saliva of infected animals through bite, scratch or licking of broken skin or a mucous membrane. Infection can be prevented by timely prevention (wash for several minutes, antisepsis and vaccination completed by antirabies immunoglobulins [Ig] according to the severity of exposure). The 55,000 human deaths estimated annually worldwide result mainly from uncontrolled canine rabies in enzootic countries (particularly in Africa and in Asia), attributable to a lack of resources or interest for this disease. Bat rabies, henceforth first cause of human's rabies in many countries in America, affects a very small number of individuals but seems more difficult to control. Shortened vaccine protocols, rationalized use of Ig and development of products of substitution should enhance access of exposed patients to prevention. Finally, research on the biological cycle, the pathogeny and on escape of virus-induced mechanisms from the immune system should continue to pave the way for presently unknown treatments of clinical rabies.
Topics: Animals; Dog Diseases; Dogs; France; Humans; Lyssavirus; Post-Exposure Prophylaxis; Rabies; Rabies Vaccines; Rabies virus; Saliva; Zoonoses
PubMed: 23351694
DOI: 10.1051/medsci/2013291013 -
International Journal of Molecular... Jan 2018Bat rabies cases in Europe are mainly attributed to two lyssaviruses, namely European Bat Lyssavirus 1 (EBLV-1) and European Bat Lyssavirus 2 (EBLV-2). Prior to the... (Review)
Review
Bat rabies cases in Europe are mainly attributed to two lyssaviruses, namely European Bat Lyssavirus 1 (EBLV-1) and European Bat Lyssavirus 2 (EBLV-2). Prior to the death of a bat worker in Finland in 1985, very few bat rabies cases were reported. Enhanced surveillance in the two subsequent years (1986-1987) identified 263 cases (more than a fifth of all reported cases to date). Between 1977 and 2016, 1183 cases of bat rabies were reported, with the vast majority (>97%) being attributed to EBLV-1. In contrast, there have been only 39 suspected cases of EBLV-2, of which 34 have been confirmed by virus typing and presently restricted to just two bat species; and . The limited number of EBLV-2 cases in Europe prompted the establishment of a network of European reference laboratories to collate all available viruses and data. Despite the relatively low number of EBLV-2 cases, a large amount of anomalous data has been published in the scientific literature, which we have here reviewed and clarified. In this review, 29 EBLV-2 full genome sequences have been analysed to further our understanding of the diversity and molecular evolution of EBLV-2 in Europe. Analysis of the 29 complete EBLV-2 genome sequences clearly corroborated geographical relationships with all EBLV-2 sequences clustering at the country level irrespective of the gene studied. Further geographical clustering was also observed at a local level. There are high levels of homogeneity within the EBLV-2 species with nucleotide identities ranging from 95.5-100% and amino acid identities between 98.7% and 100%, despite the widespread distribution of the isolates both geographically and chronologically. The mean substitution rate for EBLV-2 across the five concatenated genes was 1.65 × 10, and evolutionary clock analysis confirms the slow evolution of EBLV-2 both between and within countries in Europe. This is further supported by the first detailed EBLV-2 intra-roost genomic analysis whereby a relatively high sequence homogeneity was found across the genomes of three EBLV-2 isolates obtained several years apart (2007, 2008, and 2014) from at the same site (Stokesay Castle, Shropshire, UK).
Topics: Animals; Evolution, Molecular; Genome, Viral; Humans; Lyssavirus; Philology; Rhabdoviridae Infections
PubMed: 29303971
DOI: 10.3390/ijms19010156