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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 -
Nature Reviews. Microbiology Jan 2010Rabies virus, the prototypical neurotropic virus, causes one of the most lethal zoonotic diseases. According to official estimates, over 55,000 people die of the disease... (Review)
Review
Rabies virus, the prototypical neurotropic virus, causes one of the most lethal zoonotic diseases. According to official estimates, over 55,000 people die of the disease annually, but this is probably a severe underestimation. A combination of virulence factors enables the virus to enter neurons at peripheral sites and travel through the spinal cord to the brain of the infected host, where it often induces aggression that facilitates the transfer of the virus to a new host. This Review summarizes the current knowledge of the replication cycle of rabies virus and virus- host cell interactions, both of which are fundamental elements in our quest to understand the life cycle of rabies virus and the pathogenesis of rabies.
Topics: Animals; Brain; Humans; Models, Biological; Peripheral Nervous System; Rabies virus; Spinal Cord; Viral Proteins; Virulence Factors
PubMed: 19946287
DOI: 10.1038/nrmicro2260 -
Virus Research Apr 2019Rabies virus (RABV), an enveloped virus with a single-stranded and negative-sense RNA genome, is the type species of the Lyssavirus Genus within the Rhabdoviridae... (Review)
Review
Rabies virus (RABV), an enveloped virus with a single-stranded and negative-sense RNA genome, is the type species of the Lyssavirus Genus within the Rhabdoviridae family. As the causative agent of rabies with a nearly 100% fatality, the neurotropic RABV pose a serious threat to the global public health. Though a great effort has been made toward understanding the molecular mechanism underlying virus infection cycle, there are still many aspects need to be elucidated, especially on the early events during virus replication cycle. With the application of the multiple advanced technologies, much progress has been made on these aspects. To date, multiple receptors, such as nAChR, NCAM, p75NTR, mGluR2, carbohydrates, and gangliosides, have been identified. Following initial attachment, RABV internalization occurs through clathrin-mediated endocytosis (CME) with the help of actin. After viral entry, intracellular trafficking occurs. Two retrograde trafficking models, stating that either whole virions are parceled into vesicles or only the viral capsids are transported, have been proposed. Moreover, complete enveloped virions or G-containing vesicle-associated ribonucleoproteins (RNPs) may be formed during anterograde transport, which remains poorly characterized but is important for viral budding. Combining the data elucidating the molecular mechanisms of RABV attachment, entry, and intracellular trafficking, this review provides an integrated view of the early events in the viral life cycle.
Topics: Biological Transport; Rabies virus; Virus Internalization
PubMed: 30772332
DOI: 10.1016/j.virusres.2019.02.006 -
Advances in Virus Research 1970
Review
Topics: Antigens; Centrifugation, Density Gradient; Cesium; Chlorides; Chromatography, Ion Exchange; Complement Fixation Tests; Culture Techniques; Cytopathogenic Effect, Viral; Fluorescent Antibody Technique; Hemagglutination Tests; Hemagglutinins, Viral; Microscopy, Electron; Molecular Weight; Nucleoproteins; Phosphotungstic Acid; RNA, Viral; Rabies; Rabies Vaccines; Rabies virus; Staining and Labeling; Viral Proteins
PubMed: 4100061
DOI: No ID Found -
Molecular Membrane Biology 1999Rabies virus is a member of the rhabdovirus family. It enters cells by a process of receptor mediated endocytosis. Following this step, the viral envelope fuses with the... (Review)
Review
Rabies virus is a member of the rhabdovirus family. It enters cells by a process of receptor mediated endocytosis. Following this step, the viral envelope fuses with the endosomal membrane to allow release of the viral nucleocapsid into the cytoplasm. Fusion is induced by the low pH of the endosomal compartment and is mediated by the single viral glycoprotein G, a homotrimeric integral membrane protein. Rabies virus fusion properties are related to different conformational states of G. By different biochemical and biophysical approaches, it has been demonstrated that G can assume at least three different states: the native (N) state detected at the viral surface above pH 7, the activated (A) hydrophobic state which interacts with the target membrane as a first step of the fusion process, and the fusion inactive (I) conformation. Differently from other fusogenic viruses for which low pH-induced conformational changes are irreversible, there is a pH dependent equilibrium between these states, the equilibrium being shifted toward the I-state at low pH. The objective of this review is to detail recent findings on rhabdovirus-induced membrane fusion and to underline the differences that exist between this viral family and influenza virus which is the best known fusogenic virus. These differences have to be taken into consideration if one wants to have a global understanding of virus-induced membrane fusion.
Topics: Hydrogen-Ion Concentration; Models, Biological; Mutagenesis; Protein Conformation; Rabies virus; Viral Fusion Proteins; Viral Matrix Proteins
PubMed: 10332734
DOI: 10.1080/096876899294724 -
Advances in Virus Research 2011Rabies, a neurological disease associated with replication in central nervous system (CNS) tissues of any of a number of rabies viruses endemic in nature, is generally... (Review)
Review
Rabies, a neurological disease associated with replication in central nervous system (CNS) tissues of any of a number of rabies viruses endemic in nature, is generally fatal. Prophylactic medical intervention is immune mediated and directed at preventing the spread of the virus from a peripheral site of exposure to the CNS. While individuals rarely develop immune responses capable of clearing the virus from CNS tissues, a variety of laboratory-attenuated rabies viruses are readily cleared from the CNS tissues in animal models. By comparing immune responses to wild-type and attenuated rabies viruses in these models, we have discovered that the latter induce processes required for immune effector infiltration into CNS tissues that are absent from lethal infections. Predominant among these are activities of cells of the neurovascular unit (NVU) that promote an interaction with circulating immune cells. In the absence of this interaction, the specialized barrier function of the NVU remains intact and circulating virus-specific immune effectors are largely excluded from infected CNS tissues. Studies of mixed infections with wild-type and attenuated rabies viruses reveal that wild-type rabies viruses fail to trigger, rather than inhibit, the interactions between immune cells and the NVU required for virus clearance from the CNS. These studies provide insights into how immune effectors with the capacity to clear the virus may be delivered into CNS tissues to contain a wild-type rabies virus infection. However, to apply immunotherapeutic strategies beyond the initial stages of CNS infection, further insights into the fate of the infected cells during virus clearance are needed.
Topics: Animals; Central Nervous System; Disease Models, Animal; Dogs; Humans; Immune Evasion; Immunity, Cellular; Immunity, Humoral; Rabies virus; Virulence
PubMed: 21601042
DOI: 10.1016/B978-0-12-387040-7.00004-4 -
The Journal of General Virology Aug 2019Rabies virus causes an invariably fatal encephalitis following the onset of clinical disease. Despite the availability of safe and effective vaccines, the clinical... (Review)
Review
Rabies virus causes an invariably fatal encephalitis following the onset of clinical disease. Despite the availability of safe and effective vaccines, the clinical stages of rabies encephalitis remain untreatable, with few survivors being documented. A principal obstacle to the treatment of rabies is the neurotropic nature of the virus, with the blood-brain barrier size exclusion limit rendering the delivery of antiviral drugs and molecules to the central nervous system inherently problematic. This review focuses on efforts to try and overcome barriers to molecule delivery to treat clinical rabies and overviews current progress in the development of experimental live rabies virus vaccines that may have future applications in the treatment of clinical rabies, including the attenuation of rabies virus vectors through either the duplication or mutation of existing genes or the incorporation of non-viral elements within the genome. Rabies post-infection treatment (PIT) remains the holy grail of rabies research.
Topics: Animals; Antiviral Agents; Central Nervous System Infections; Humans; Rabies; Rabies virus
PubMed: 31237530
DOI: 10.1099/jgv.0.001269 -
The Onderstepoort Journal of Veterinary... Dec 1993
Review
Topics: Amino Acid Sequence; Animals; Antibodies, Monoclonal; Epitopes; RNA, Viral; Rabies virus
PubMed: 7539906
DOI: No ID Found -
Nihon Rinsho. Japanese Journal of... Mar 2003
Review
Topics: Animals; Diagnosis, Differential; GTP-Binding Proteins; Genome, Viral; Humans; Molecular Diagnostic Techniques; Phylogeny; Rabies; Rabies virus; Reverse Transcriptase Polymerase Chain Reaction; Viral Proteins
PubMed: 12718023
DOI: No ID Found -
Advances in Virus Research 2011Until recently, single-stranded negative sense RNA viruses (ssNSVs) were one of only a few important human viral pathogens, which could not be created from cDNA. The... (Review)
Review
Until recently, single-stranded negative sense RNA viruses (ssNSVs) were one of only a few important human viral pathogens, which could not be created from cDNA. The inability to manipulate their genomes hindered their detailed genetic analysis. A key paper from Conzelmann's laboratory in 1994 changed this with the publication of a method to recover rabies virus (RABV) from cDNA. This discovery not only dramatically changed the broader field of ssNSV biology but also opened a whole new avenue for studying RABV pathogenicity, developing novel RABV vaccines as well a new generation of RABV-based vaccine vectors, and creating research tools important in neuroscience such as neuronal tracing.
Topics: Animals; Drug Carriers; Genetic Engineering; Genetic Vectors; Genetics, Microbial; Humans; Rabies virus; Viral Vaccines
PubMed: 21601047
DOI: 10.1016/B978-0-12-387040-7.00009-3