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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 -
The Veterinary Clinics of North... Apr 1997Equine rabies is a sporadic but highly fatal zoonotic disease. The disease persists in wildlife populations throughout the United States, Canada, Mexico, and other parts... (Review)
Review
Equine rabies is a sporadic but highly fatal zoonotic disease. The disease persists in wildlife populations throughout the United States, Canada, Mexico, and other parts of the world. It remains a threat to all domestic species, including the horse. This article reports recent advances in the molecular virology of the rabies virus and its pathogenesis, and it also reviews the history, clinical signs, diagnostic tests, vaccination protocols, and postexposure management recommendations for the equine species.
Topics: Animals; Horse Diseases; Horses; Rabies; Rabies Vaccines; Rabies virus; United States
PubMed: 9106339
DOI: 10.1016/s0749-0739(17)30251-1 -
The Yale Journal of Biology and Medicine 1982Five viruses related to rabies occur in Africa. Two of these, Obodhiang from Sudan and kotonkan from Nigeria, were found in insects and are only distantly related to... (Review)
Review
Five viruses related to rabies occur in Africa. Two of these, Obodhiang from Sudan and kotonkan from Nigeria, were found in insects and are only distantly related to rabies virus. The other three are antigenically more closely related to rabies. Mokola virus was isolated from shrews in Nigeria, Lagos bat virus from fruit bats in Nigeria, and Duvenhage virus from brain of a man bitten by a bat in South Africa. The public health significance of the rabies-related viruses was emphasized in Zimbabwe where in 1981 a rabies-related virus became epizootic in the dog and cat population. It is postulated that the ancestral origin of rabies virus was Africa where the greatest antigenic diversity occurs and that the ancestor may have been an insect virus. Questions are raised why rabies has not evolved more rapidly in the New World, given the frequency and ease with which antigenic changes can be induced in the laboratory, and how the virus became so extensively established in New World bats.
Topics: Africa; Animals; Antigens, Viral; Biological Evolution; Chiroptera; Cross Reactions; Insecta; Rabies virus; Rhabdoviridae; Shrews; Virus Diseases
PubMed: 6758373
DOI: No ID Found -
International Journal of Infectious... Aug 2014The number of wildlife rabies and wildlife-associated human and livestock rabies cases has increased in recent years, particularly in the southeast and northeast regions... (Review)
Review
The number of wildlife rabies and wildlife-associated human and livestock rabies cases has increased in recent years, particularly in the southeast and northeast regions of mainland China. To better understand wildlife rabies and its role in human and livestock rabies, we reviewed what is known about wildlife rabies from the 1990s to 2013 in mainland China. In addition, the genetic diversity and phylogeny of available wildlife-originated rabies viruses (RABVs) were analyzed. Several wildlife species carry rabies including the bat, Chinese ferret badger, raccoon dog, rat, fox, and wolf. RABVs have been isolated or detected in the bat, Chinese ferret badger, raccoon dog, Apodemus, deer, and vole. Among them, the bat, Chinese ferret badger, and raccoon dog may play a role in the ecology of lyssaviruses in mainland China. All wildlife-originated RABVs were found to belong to genotype 1 RABV except for a bat-originated Irkut virus isolated in 2012. Several substitutions were found between the glycoprotein of wildlife-originated RABVs and vaccine strains. Whether these substitutions could affect the efficacy of currently used vaccines against infections caused by these wildlife-originated RABVs needs to be investigated further. Phylogenetic analysis showed that RABVs in the bat, Chinese ferret badger, and raccoon dog were distinct from local dog-originated RABVs, and almost all collected wildlife-originated isolates were associated with older China clades II to V, suggesting the possibility of wildlife reservoirs in mainland China through the ages.
Topics: Animal Diseases; Animals; Animals, Wild; China; History, 20th Century; History, 21st Century; Humans; Livestock; Rabies; Rabies virus
PubMed: 24911887
DOI: 10.1016/j.ijid.2014.04.016 -
PLoS Pathogens Dec 2022Rabies virus (RABV) transcription and replication take place within viral factories having liquid properties, called Negri bodies (NBs), that are formed by liquid-liquid...
Rabies virus (RABV) transcription and replication take place within viral factories having liquid properties, called Negri bodies (NBs), that are formed by liquid-liquid phase separation (LLPS). The co-expression of RABV nucleoprotein (N) and phosphoprotein (P) in mammalian cells is sufficient to induce the formation of cytoplasmic biocondensates having properties that are like those of NBs. This cellular minimal system was previously used to identify P domains that are essential for biocondensates formation. Here, we constructed fluorescent versions of N and analyzed by FRAP their dynamics inside the biocondensates formed in this minimal system as well as in NBs of RABV-infected cells using FRAP. The behavior of N appears to be different of P as there was no fluorescence recovery of N proteins after photobleaching. We also identified arginine residues as well as two exposed loops of N involved in condensates formation. Corresponding N mutants exhibited distinct phenotypes in infected cells ranging from co-localization with NBs to exclusion from them associated with a dominant-negative effect on infection. We also demonstrated that in vitro, in crowded environments, purified P as well as purified N0-P complex (in which N is RNA-free) form liquid condensates. We identified P domains required for LLPS in this acellular system. P condensates were shown to associate with liposomes, concentrate RNA, and undergo a liquid-gel transition upon ageing. Conversely, N0-P droplets were disrupted upon incubation with RNA. Taken together, our data emphasize the central role of P in NBs formation and reveal some physicochemical features of P and N0-P droplets relevant for explaining NBs properties such as their envelopment by cellular membranes at late stages of infection and nucleocapsids ejections from the viral factories.
Topics: Animals; Rabies virus; Nucleoproteins; Rabies; Nucleocapsid; Phosphoproteins; Virus Replication; Mammals
PubMed: 36480574
DOI: 10.1371/journal.ppat.1011022 -
PloS One 2021Rabies spreads in both Arctic (Vulpes lagopus) and red foxes (Vulpes vulpes) throughout the Canadian Arctic but limited wildlife disease surveillance, due to the...
Rabies spreads in both Arctic (Vulpes lagopus) and red foxes (Vulpes vulpes) throughout the Canadian Arctic but limited wildlife disease surveillance, due to the extensive landmass of the Canadian north and its small widely scattered human population, undermines our knowledge of disease transmission patterns. This study has explored genetic population structure in both the rabies virus and its fox hosts to better understand factors that impact rabies spread. Phylogenetic analysis of 278 samples of the Arctic lineage of rabies virus recovered over 40 years identified four sub-lineages, A1 to A4. The A1 lineage has been restricted to southern regions of the Canadian province of Ontario. The A2 lineage, which predominates in Siberia, has also spread to northern Alaska while the A4 lineage was recovered from southern Alaska only. The A3 sub-lineage, which was also found in northern Alaska, has been responsible for virtually all cases across northern Canada and Greenland, where it further differentiated into 18 groups which have systematically evolved from a common predecessor since 1975. In areas of Arctic and red fox sympatry, viral groups appear to circulate in both hosts, but both mitochondrial DNA control region sequences and 9-locus microsatellite genotypes revealed contrasting phylogeographic patterns for the two fox species. Among 157 Arctic foxes, 33 mitochondrial control region haplotypes were identified but little genetic structure differentiating localities was detected. Among 162 red foxes, 18 control region haplotypes delineated three groups which discriminated among the Churchill region of Manitoba, northern Quebec and Labrador populations, and the coastal Labrador locality of Cartwright. Microsatellite analyses demonstrated some genetic heterogeneity among sampling localities of Arctic foxes but no obvious pattern, while two or three clusters of red foxes suggested some admixture between the Churchill and Quebec-Labrador regions but uniqueness of the Cartwright group. The limited population structure of Arctic foxes is consistent with the rapid spread of rabies virus subtypes throughout the north, while red fox population substructure suggests that disease spread in this host moves most readily down certain independent corridors such as the northeastern coast of Canada and the central interior. Interestingly the evidence suggests that these red fox populations have limited capacity to maintain the virus over the long term, but they may contribute to viral persistence in areas of red and Arctic fox sympatry.
Topics: Animals; Canada; DNA, Mitochondrial; Foxes; Genotype; Microsatellite Repeats; Phylogeny; Rabies virus
PubMed: 33592018
DOI: 10.1371/journal.pone.0246508 -
Revue Scientifique Et Technique... Aug 2018Rabies is an ancient zoonotic disease caused by infection with the rabies virus (RABV). While the circulation of RABV in domestic dogs has been appreciated for...
Rabies is an ancient zoonotic disease caused by infection with the rabies virus (RABV). While the circulation of RABV in domestic dogs has been appreciated for centuries, the recognition of bat and wild carnivore reservoirs began in the early part of the 20th century. Bats are the ancestral reservoir of RABV and a remarkable diversity of species perpetuate distinct lineages of the virus, despite the fact that circulation in bats is geographically limited to the New World fauna. The circulation of RABV in domestic dogs likely represents a historic shift from a bat reservoir, although the timing and details of such an ancient event have been difficult to resolve from the virus genetic evidence. Since becoming established in the domestic dog population, RABV has undergone repeated host shifts to wild carnivores globally. These shifts have most frequently been to species within families of the Caniformia suborder of carnivores. The circulation of RABV in bats has been linked to host shifts to wild carnivore reservoirs in North and South America. It is clear that RABV has been incredibly successful at exploiting diverse chiropteran and carnivore hosts. With improved control of circulation in domestic dogs, surveillance is likely to yield additional discoveries regarding the diversity of wildlife reservoirs and vectors of RABV.
Topics: Animals; Animals, Domestic; Animals, Wild; Chiroptera; Disease Reservoirs; Dogs; North America; Rabies; Rabies virus; South America; Zoonoses
PubMed: 30747141
DOI: 10.20506/rst.37.2.2808 -
Biochimica Et Biophysica Acta.... Dec 2020Viruses reshape the organization of the cell interior to achieve different steps of their cellular cycle. Particularly, viral replication and assembly often take place... (Review)
Review
Viruses reshape the organization of the cell interior to achieve different steps of their cellular cycle. Particularly, viral replication and assembly often take place in viral factories where specific viral and cellular proteins as well as nucleic acids concentrate. Viral factories can be either membrane-delimited or devoid of any cellular membranes. In the latter case, they are referred as membrane-less replication compartments. The most emblematic ones are the Negri bodies, which are inclusion bodies that constitute the hallmark of rabies virus infection. Interestingly, Negri bodies and several other viral replication compartments have been shown to arise from a liquid-liquid phase separation process and, thus, constitute a new class of liquid organelles. This is a paradigm shift in the field of virus replication. Here, we review the different aspects of membrane-less virus replication compartments with a focus on the Mononegavirales order and discuss their interactions with the host cell machineries and the cytoskeleton. We particularly examine the interplay between viral factories and the cellular innate immune response, of which several components also form membrane-less condensates in infected cells.
Topics: Cell Membrane; Inclusion Bodies, Viral; Rabies; Rabies virus; Viral Proteins; Viral Replication Compartments; Virus Replication
PubMed: 32835749
DOI: 10.1016/j.bbamcr.2020.118831 -
Viruses Aug 2016Rabies has affected mankind for several centuries and is one of the oldest known zoonoses. It is peculiar how little is known regarding the means by which rabies virus... (Review)
Review
Rabies has affected mankind for several centuries and is one of the oldest known zoonoses. It is peculiar how little is known regarding the means by which rabies virus (RABV) evades the immune response and kills its host. This review investigates the complex interplay between RABV and the immune system, including the various means by which RABV evades, or advantageously utilizes, the host immune response in order to ensure successful replication and spread to another host. Different factors that influence immune responses-including age, sex, cerebral lateralization and temperature-are discussed, with specific reference to RABV and the effects on host morbidity and mortality. We also investigate the role of apoptosis and discuss whether it is a detrimental or beneficial mechanism of the host's response to infection. The various RABV proteins and their roles in immune evasion are examined in depth with reference to important domains and the downstream effects of these interactions. Lastly, an overview of the means by which RABV evades important immune responses is provided. The research discussed in this review will be important in determining the roles of the immune response during RABV infections as well as to highlight important therapeutic target regions and potential strategies for rabies treatment.
Topics: Animals; Host-Pathogen Interactions; Humans; Immune Evasion; Rabies virus; Virus Replication
PubMed: 27548204
DOI: 10.3390/v8080231 -
Journal of Virology May 2023Viral protein assembly and virion budding are tightly regulated to enable the proper formation of progeny virions. At this late stage in the virus life cycle, some...
Viral protein assembly and virion budding are tightly regulated to enable the proper formation of progeny virions. At this late stage in the virus life cycle, some enveloped viruses take advantage of the host endosomal sorting complex required for transport (ESCRT) machinery, which contributes to the physiological functions of membrane modulation and abscission. Bullet-shaped viral particles are unique morphological characteristics of rhabdoviruses; however, the involvement of host factors in rhabdovirus infection and, specifically, the molecular mechanisms underlying virion formation are not fully understood. In the present study, we used a small interfering RNA (siRNA) screening approach and found that the ESCRT-I component TSG101 contributes to the propagation of rabies virus (RABV). We demonstrated that the matrix protein (M) of RABV interacts with TSG101 via the late domain containing the PY and YL motifs, which are conserved in various viral proteins. Loss of the YL motif in the RABV M or the downregulation of host TSG101 expression resulted in the intracellular aggregation of viral proteins and abnormal virus particle formation, indicating a defect in the RABV assembly and budding processes. These results indicate that the interaction of the RABV M and TSG101 is pivotal for not only the efficient budding of progeny RABV from infected cells but also for the bullet-shaped virion morphology. Enveloped viruses bud from cells with the host lipid bilayer. Generally, the membrane modulation and abscission are mediated by host ESCRT complexes. Some enveloped viruses utilize their late (L-) domain to interact with ESCRTs, which promotes viral budding. Rhabdoviruses form characteristic bullet-shaped enveloped virions, but the underlying molecular mechanisms involved remain elusive. Here, we showed that TSG101, one of the ESCRT components, supports rabies virus (RABV) budding and proliferation. TSG101 interacted with RABV matrix protein via the L-domain, and the absence of this interaction resulted in intracellular virion accumulation and distortion of the morphology of progeny virions. Our study reveals that virion formation of RABV is highly regulated by TSG101 and the virus matrix protein.
Topics: Humans; Endosomal Sorting Complexes Required for Transport; Morphogenesis; Rabies; Rabies virus; Viral Proteins; Virion; Virus Release; Cell Line; Animals
PubMed: 37042780
DOI: 10.1128/jvi.00438-23