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Journal of Neurovirology Aug 2015Rabies is an ancient neurological disease that is almost invariably fatal once the clinical symptoms develop. Currently, prompt wound cleansing after exposing to a...
Rabies is an ancient neurological disease that is almost invariably fatal once the clinical symptoms develop. Currently, prompt wound cleansing after exposing to a potentially rabid animal and vaccination using rabies vaccine combined with administration of rabies immune globulin are the only effective methods for post-exposure prophylaxis against rabies. Reverse genetic technique is a novel approach to investigate the function of a specific gene by analyzing the phenotypic effects through directly manipulating the gene sequences. It has revolutionized and provided a powerful tool to study the molecular biology of RNA viruses and has been widely used in rabies virus research. The attenuation of rabies virus virulence is the prerequisite for rabies vaccine development. Given the current challenge that sufficient and affordable high-quality vaccines are limited and lacking for global rabies prevention and control, highly cell-adapted, stable, and attenuated rabies viruses with broad cross-reactivity against different viral variants are ideal candidates for consideration to meet the need for human rabies control in the future. A number of approaches have been pursued to reduce the virulence of the virus and improve the safety of rabies vaccines. The application of reverse genetic technique has greatly advanced the engineering of rabies virus and paves the avenue for utilizing rabies virus for vaccine against rabies, viral vectors for exogenous antigen expression, and gene therapy in the future.
Topics: Animals; Humans; Rabies Vaccines; Rabies virus; Reverse Genetics; Virulence
PubMed: 25994916
DOI: 10.1007/s13365-015-0350-2 -
Advances in Virus Research 2011The host response to infection generally begins with interactions between pathogen-associated molecular patterns common to a variety of infectious agents and reciprocal... (Review)
Review
The host response to infection generally begins with interactions between pathogen-associated molecular patterns common to a variety of infectious agents and reciprocal pattern-recognition receptors (PRRs) expressed by cells of the innate immune system. The innate responses triggered by these interactions contribute to the early, innate control of infection as well as the induction of pathogen-specific adaptive immunity. The outcome of infection with wild-type rabies virus is particularly dependent upon the rapid induction of innate and adaptive immune mechanisms that can prevent the virus from reaching central nervous system (CNS) tissues, where it can evade immune clearance. However, laboratory strains that reach the CNS can be cleared, and this has evidently occurred in individuals with rabies. Therefore, PRRs may be active in the periphery and the CNS during rabies virus infection, possibly depending upon the nature of the infecting virus. To investigate these possibilities, we first examined the outcome of infection with attenuated rabies virus in mice lacking MyD88, an adaptor protein that is used to activate the transcription factor NF-κB by a number of PRRs including all of the Toll-like receptors (TLRs) except for TLR3. Finding that attenuated rabies virus mediates lethal disease in the absence of MyD88, we then examined the effects of the deletion of receptors using MyD88 including TLRs 2, 4, 7, and 9 as well as IL-1-receptor 1, and IFN-αβR on infection. Only mice lacking TLR7 exhibited a phenotype, with mortality intermediate between MyD88(-/-) and control mice with deficits in both the development of peripheral immunity and rabies virus clearance from the CNS.
Topics: Animals; Disease Models, Animal; Host-Pathogen Interactions; Humans; Mice; Rabies; Rabies virus; Toll-Like Receptors; Virulence
PubMed: 21601045
DOI: 10.1016/B978-0-12-387040-7.00007-X -
Journal of Virology Dec 1968Goose erythrocytes were agglutinated by five strains of rabies virus grown in monolayer cell cultures at pH 6.4 and at 0 to 4 C. Hemagglutination was not affected by the...
Goose erythrocytes were agglutinated by five strains of rabies virus grown in monolayer cell cultures at pH 6.4 and at 0 to 4 C. Hemagglutination was not affected by the cell type in which the virus was grown. Prerequisites for occurrence of hemagglutination are absence of hemagglutination inhibitors (such as those contained in bovine serum) and a relatively high virus concentration (> 10(6) plaque-forming units of virus per ml). "Soluble" hemagglutinin was not present in crude preparations of extracellular virus. Treatment of purified preparations of extracellular virus with Tween 80 and ether did not result in release of a "soluble" hemagglutinin. The hemagglutinating property of extracellular virus seemed to be conditioned by the integrity of its coat. Preparations of infectious intracellular virus exhibited about 15 times lower hemagglutinating activity than extracellular virus. This decreased hemagglutinating activity did not seem to be caused by binding of hemagglutination inhibitors to the virus particles. Rabies virus can be quantitatively adsorbed onto and eluted from erythrocytes. Erythrocytes pretreated with rabies virus retained their ability to be agglutinated by the same virus strain. The reaction with rabies virus of erythrocytes treated with the receptor-destroying enzyme or KIO(4) was the same as that of nontreated erythrocytes. The hemagglutinating component of rabies virus, therefore, does not exhibit neuraminidase activity. Treatment of extracellular virus by various agents indicated that the hemagglutinating component consists of protein or lipoprotein. Sulfhydryl groups present in the viral hemagglutinin are essential for hemagglutination.
Topics: Animals; Cell Line; Centrifugation, Density Gradient; Complement Fixation Tests; Cricetinae; Culture Techniques; Erythrocytes; Geese; Hemagglutination, Viral; Humans; Hydrogen-Ion Concentration; Indicators and Reagents; Lung; Mice; Rabies virus; Temperature; Virus Cultivation
PubMed: 5754504
DOI: 10.1128/JVI.2.12.1381-1392.1968 -
Virus Research Jul 2005The direct fluorescent antibody test is a sensitive and specific procedure used in the routine diagnosis of rabies. However, given the critical role of the rabies... (Review)
Review
The direct fluorescent antibody test is a sensitive and specific procedure used in the routine diagnosis of rabies. However, given the critical role of the rabies diagnostic laboratory in patient management and public health decision-making, the use of a standardized national rabies diagnostic procedure is highly recommended. Seemingly small variations in test procedures may have dramatic effects on sensitivity. For example, two independent reports of diminished staining performance of two lots of a commercial anti-rabies conjugate were investigated in this study. The diminished staining occurred only with a single rabies-virus variant, associated with big brown bats, Eptesicus fuscus, in the southwestern United States. Similarly diluted and prepared diagnostic reagents provided bright staining on all other variants of rabies-virus tested. Subsequent evaluation disclosed that the phenomenon was associated with the relative concentrations of glycerol used in the mounting media by the reporting laboratories. These findings, related to the proper selection of an optimal cover-glass mountant for use in the immunofluorescence procedure, demonstrate the potential for erroneous results with severe implications for patient health, when uncontrolled variations in protocol occur. This paper underscores the necessity for all rabies diagnostic laboratories to follow one standard protocol. Such a protocol has been placed on the websites maintained by the Centers for Disease Control and Prevention: .
Topics: Antigens, Viral; Fluorescent Antibody Technique; Humans; Laboratories; Quality Assurance, Health Care; Rabies; Rabies virus; Reagent Kits, Diagnostic
PubMed: 15896406
DOI: 10.1016/j.virusres.2005.03.014 -
Advances in Virus Research 1993
Review
Topics: Animals; Humans; Nervous System; Rabies; Rabies virus; Virulence
PubMed: 8430523
DOI: 10.1016/s0065-3527(08)60090-1 -
The Lancet. Infectious Diseases Jun 2002Rabies is an acute, progressive, incurable viral encephalitis. The causative agents are neurotropic RNA viruses in the family Rhabdoviridae, genus Lyssavirus. Mammalian... (Review)
Review
Rabies is an acute, progressive, incurable viral encephalitis. The causative agents are neurotropic RNA viruses in the family Rhabdoviridae, genus Lyssavirus. Mammalian reservoirs include the Carnivora and Chiroptera, but rabid dogs still pose the greatest hazard worldwide. Viral transmission occurs mainly via animal bite, and once the virus is deposited in peripheral wounds, centripetal passage occurs towards the central nervous system. After viral replication, there is centrifugal spread to major exit portals, the salivary glands. The epidemiological significance of any host "carrier" state remains highly speculative. Although incubation periods average 1-3 months, disease occurrence days or years after exposure has been documented. Rabies should be suspected in patients with a concomitant history of animal bite and traditional clinical presentation, but a lack of such clues makes antemortem diagnosis a challenge. Pathogenetic mechanisms remain poorly understood, and current care entails palliative measures only. Current medical emphasis relies heavily on prevention of exposure and intervention before clinical onset. Prophylaxis encompasses thorough wound treatment, vaccine administration, and inoculation of rabies immunoglobulin. Although it is a major zoonosis, canine rabies can be eliminated, and application of new vaccine technologies permits significant disease control among wildlife species. Nevertheless, despite much technical progress in the past century, rabies is a disease of neglect and presents a modern public-health conundrum.
Topics: Animals; Brain; Disease Vectors; Dogs; Global Health; Humans; Rabies; Rabies Vaccines; Rabies virus
PubMed: 12144896
DOI: 10.1016/s1473-3099(02)00287-6 -
Contributions To Microbiology and... 1987
Review
Topics: Amino Acid Sequence; Animals; Antigens, Viral; Genes, Viral; Genetic Variation; Humans; Mutation; Rabies; Rabies virus; T-Lymphocytes; Viral Proteins
PubMed: 3304828
DOI: No ID Found -
Uirusu Dec 2007Rabies virus causes lethal neurological symptoms in humans and animals. Rabies epidemics have continued to occur throughout the world, despite the fact that rabies can... (Review)
Review
Rabies virus causes lethal neurological symptoms in humans and animals. Rabies epidemics have continued to occur throughout the world, despite the fact that rabies can be effectively prevented by vaccination. The development of inexpensive and safe attenuated live vaccines and the establishment of cures are the keys to control rabies. To achieve these objectives, it is important to elucidate mechanism by which rabies virus causes disease. Here, previous studies on the pathogenesis of rabies virus are reviewed and ways to apply previous findings to rabies control are also discussed.
Topics: Amino Acid Sequence; Animals; Dogs; GTP-Binding Proteins; Humans; Rabies; Rabies Vaccines; Rabies virus; Vaccines, Attenuated; Viral Proteins; Virulence
PubMed: 18357757
DOI: 10.2222/jsv.57.191 -
Research in Veterinary Science Aug 2002Rabies remains as one of the most feared zoonotic diseases in the world. All warm-blooded animals are susceptible to infection by the virus, but the main vectors of... (Review)
Review
Rabies remains as one of the most feared zoonotic diseases in the world. All warm-blooded animals are susceptible to infection by the virus, but the main vectors of human infection are dogs and cats. The control of rabies largely depends on the prevention of infection of dogs and cats by vaccination in endemic areas and the control of their movement, including measures of quarantine and vaccination, in rabies-free countries. This paper provides an overview on recent developments in rabies, with particular emphasis on the epidemiology, pathogenesis, diagnosis, and control.
Topics: Animals; Humans; Rabies; Rabies Vaccines; Rabies virus
PubMed: 12208103
DOI: 10.1016/s0034-5288(02)00046-2 -
Virus Genes Oct 2019Rabies is endemic in Zambia and Zimbabwe. The previously investigated strains of rabies virus in central Zambia belong to the Africa 1b lineage, with similar circulating...
Rabies is endemic in Zambia and Zimbabwe. The previously investigated strains of rabies virus in central Zambia belong to the Africa 1b lineage, with similar circulating virus strains found in the various tested hosts and regions. However, prior work assessed only limited regions and host species. Thus, this study aimed to more comprehensively determine the genetic diversity of rabies virus across regions of Zambia and Zimbabwe. RNA (n = 76) was extracted from positive direct fluorescent antibody test brain tissues from dog, cow, goat, cat, pig, human, and jackal collected from Zambia and Zimbabwe. The amplicons of the nucleoprotein and glycoprotein genes were obtained from all examined samples by nested RT-PCR and subsequently sequenced. A phylogenetic analysis of the N gene confirmed that all the endemic strains of rabies virus in Zambia and Zimbabwe belong to the Africa 1b lineage. The obtained viral gene sequences were phylogenetically divided into two clusters. Cluster II comprised only Zambian strains. In contrast, cluster I comprised both Zambia and Zimbabwe strains, with strains from Zimbabwe forming a distinct lineage from Zambian strains, implying viral genetic divergence due to geographical barriers. However, no evidence of clustering based on host or region was observed, implying the circulation of similar virus strains occurs in different hosts and regions of Zambia and Zimbabwe. The clustering of rabies virus strains from jackals with those from domestic animals provides evidence of similar virus strains circulating in both wildlife and domestic animals, and that the jackal might be one of the potential reservoirs of rabies virus infection. In this study, no strains circulating in Zimbabwe were detected in Zambia.
Topics: Animals; Genetic Variation; Humans; Phylogeography; Polymerase Chain Reaction; Rabies; Rabies virus; Reverse Transcriptase Polymerase Chain Reaction; Sequence Analysis, DNA; Viral Structural Proteins; Zambia; Zimbabwe
PubMed: 31267444
DOI: 10.1007/s11262-019-01682-y