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Vaccine Dec 2012All members of the lyssavirus genus are capable of causing disease that invariably results in death following the development of clinical symptoms. The recent detection... (Review)
Review
All members of the lyssavirus genus are capable of causing disease that invariably results in death following the development of clinical symptoms. The recent detection of several novel lyssavirus species across the globe, in different animal species, has demonstrated that the lyssavirus genus contains a greater degree of genetic and antigenic variation than previously suspected. The divergence of species within the genus has led to a differentiation of lyssavirus isolates based on both antigenic and genetic data into two, and potentially a third phylogroup. Critically, from both a human and animal health perspective, current rabies vaccines appear able to protect against lyssaviruses classified within phylogroup I. However no protection is afforded against phylogroup II viruses or other more divergent viruses. Here we review current knowledge regarding the diversity and antigenicity of the lyssavirus glycoprotein. We review the degree of cross protection afforded by rabies vaccines, the genetic and antigenic divergence of the lyssaviruses and potential mechanisms for the development of novel lyssavirus vaccines for use in areas where divergent lyssaviruses are known to circulate, as well as for use by those at occupational risk from these pathogens.
Topics: Animals; Genetic Variation; Humans; Rabies; Rabies Vaccines; Rabies virus
PubMed: 23084854
DOI: 10.1016/j.vaccine.2012.10.015 -
Journal of Virological Methods May 2017Rabies virus is a notifiable pathogen that must be handled in high containment facilities where national and international guidelines apply. For the effective...
Rabies virus is a notifiable pathogen that must be handled in high containment facilities where national and international guidelines apply. For the effective inactivation of rabies virus, a number of reagents were tested. Virkon S (1%) solution caused more than 4log reduction of rabies virus in culture medium supplemented with 10% foetal calf serum within 1min. Isopropyl alcohol (70%) treatment resulted in >3log reduction of rabies virus within 20s when applied at a ratio of 19:1, making it a suitable agent for surface decontamination whereas 70% ethanol was ineffective. Rabies virus (from 10 to 10ffu/ml) was also inactivated when cell cultures were fixed with 3% or 4% paraformaldehyde for 30min. Regardless of inactivation procedure, when taking inactivated virus preparations out of a biological containment envelope, proof of inocuity must be demonstrated to cover any possible error/deviation from procedure.
Topics: Disinfectants; Microbial Viability; Rabies virus; Virus Inactivation
PubMed: 28174074
DOI: 10.1016/j.jviromet.2017.02.002 -
Cellular and Molecular Life Sciences :... Jan 2008Rabies virus is a negative-strand RNA virus. Its RNA genome is condensed by the viral nucleoprotein (N), and it is this N-RNA complex that is the template for... (Review)
Review
Rabies virus is a negative-strand RNA virus. Its RNA genome is condensed by the viral nucleoprotein (N), and it is this N-RNA complex that is the template for transcription and replication by the viral RNA-dependent RNA polymerase complex. Here we discuss structural and functional aspects of viral transcription and replication based on the atomic structure of a recombinant rabies virus N-RNA complex. We situate available biochemical data on N-RNA interactions with viral and cellular factors in the structural framework with regard to their implications for transcription and replication. Finally, we compare the structure of the rabies virus nucleoprotein with the structures of the nucleoproteins of vesicular stomatitis virus, Borna disease virus and influenza virus, highlighting potential similarities between these virus families.
Topics: Humans; Nucleoproteins; RNA, Viral; Rabies virus; Rhabdoviridae; Transcription, Genetic; Virus Replication
PubMed: 17938861
DOI: 10.1007/s00018-007-7298-1 -
Virus Research Jul 2005The RNA polymerase of rabies virus (RV) is a two-protein complex composed of L (a large catalytic component) and P (a non-catalytic phosphoprotein cofactor) proteins. We... (Review)
Review
The RNA polymerase of rabies virus (RV) is a two-protein complex composed of L (a large catalytic component) and P (a non-catalytic phosphoprotein cofactor) proteins. We generated a gene-deficient RV lacking the entire P gene from HEP-Flury (HEP) strain, one of the most attenuated RV strains, by the method of reverse genetics. This P gene-deficient (def-P) virus could replicate and produce progeny viruses with a slightly retarded rate in the cell lines that constitutively express the P protein. The def-P virus could perform the primary RNA transcription by the virion-associated polymerase even in the infected host without de novo P protein synthesis. However, the def-P virus required the newly synthesized P protein for the secondary RNA transcription and genome RNA replication of virus. No progeny virus was produced in the infected host that did not express P protein. The def-P virus was apathogenic in adult and suckling mice even when inoculated intracranially. On the other hand, inoculation of the def-P virus into mice induced a high titer of virus-neutralizing antibody and protected mice from lethal challenge with the CVS strain. These results demonstrated that the def-P virus could induce strong protective immunity against rabies virus without the production of progeny virus and the severe host damage. The def-P virus would be a potential resource of safe live-attenuated rabies vaccine.
Topics: Animals; Defective Viruses; Molecular Chaperones; Phosphoproteins; Rabies Vaccines; Rabies virus; Viral Structural Proteins; Virus Replication
PubMed: 15896403
DOI: 10.1016/j.virusres.2005.03.011 -
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 -
Virus Research Aug 2005Rabies virus (RV) is a prototype neurotropic virus that causes fatal disease in human and animals. RV infects hosts at the periphery, enters motoneurons or sensory... (Review)
Review
Rabies virus (RV) is a prototype neurotropic virus that causes fatal disease in human and animals. RV infects hosts at the periphery, enters motoneurons or sensory nerves and moves to the central nervous system (CNS) via retrograde axonal transport. At later stages, there is also centrifugal spread to major exit portals, such as the salivary glands. Transmission to other hosts is facilitated by behavioral changes related to the CNS infection. Successful accomplishment of the RV infectious cycle depends on multiple functions of the virus, and of individual virus proteins, all together defining the typical pathogenicity and virulence, i.e. the biological fitness of this virus. In particular, it appears important for RV to sneak into the host without causing pronounced host responses and to preserve, at least for some time, the integrity of infected cells and of the neuronal network. The availability of reverse genetics systems that allow generation of engineered recombinant RV has provided tools for a more detailed analysis of viral functions relevant to the typical RV pathogenesis. Novel developments such as tracking of live fluorescent RV are further increasing the opportunities to decipher RV pathogenicity factors. In this review, we describe different aspects of the molecular biology of RV that are relevant to pathogenesis, with a particular emphasis on the accurate control of RV transcription, gene expression, and replication. In addition, the role of individual virus proteins in maintaining host cell integrity and supporting retrograde transport is discussed. The potential of recombinant RVs with single or multiple pathogenicity factors eliminated is being discussed in terms of vaccine and virus vector development.
Topics: Amino Acid Sequence; Animals; Apoptosis; Axonal Transport; Cell Line; Gene Expression Regulation, Viral; Humans; Mice; Molecular Sequence Data; Neurons; Rabies virus; Virus Replication
PubMed: 15885837
DOI: 10.1016/j.virusres.2005.04.004 -
Virologica Sinica Apr 2020While host proteins incorporated into virions during viral budding from infected cell are known to play essential roles in multiple process of the life cycle of progeny...
While host proteins incorporated into virions during viral budding from infected cell are known to play essential roles in multiple process of the life cycle of progeny virus, these characteristics have been largely neglected in studies on rabies virus (RABV). Here, we purified the RABV virions with good purity and integrity, and analyzed their proteome by nano LC-MS/MS, followed by the confirmation with immunoblot and immuno-electronic microscopy. In addition to the 5 viral proteins, 49 cellular proteins were reproducibly identified to be incorporated into matured RABV virions. Function annotation suggested that 24 of them were likely involved in virus replication. Furthermore, cryo-EM was employed to observe the purified RABV virions, generating high-resolution pictures of the bullet-shaped virion structure of RABV. This study has provided new insights into the host proteins composition in RABV virion and shed the light for further investigation on molecular mechanisms of RABV infection, as well as the discovery of new anti-RABV therapeutics.
Topics: Cryoelectron Microscopy; Gene Expression Profiling; Proteomics; Rabies virus; Tandem Mass Spectrometry; Viral Proteins; Virion; Virus Replication
PubMed: 31429011
DOI: 10.1007/s12250-019-00157-6 -
The Journal of Veterinary Medical... Aug 2016Rabies is a zoonotic disease caused by the Lyssavirus rabies virus (RABV) that can infect most mammals, including humans, where it has a case-fatality rate of almost... (Review)
Review
Rabies is a zoonotic disease caused by the Lyssavirus rabies virus (RABV) that can infect most mammals, including humans, where it has a case-fatality rate of almost 100%. Although preventable by vaccination, rabies causes c. 59,000 human fatalities every year worldwide. Thus, there exists an urgent need to establish an effective therapy and/or improve dissemination of vaccines for humans and animals. These outcomes require greater understanding of the mechanisms of RABV pathogenesis to identify new molecular targets for the development of therapeutics and/or live vaccines with high levels of safety. Importantly, a number of studies in recent years have indicated that RABV specifically suppresses host immunity through diverse mechanisms and that this is a key process in pathogenicity. Here, we review current understanding of immune modulation by RABV, with an emphasis on its significance to pathogenicity and the potential exploitation of this knowledge to develop new vaccines and antivirals.
Topics: Animals; Humans; Immune Evasion; Interferons; Rabies Vaccines; Rabies virus
PubMed: 27041139
DOI: 10.1292/jvms.16-0092 -
Current Topics in Microbiology and... 1994
Review
Topics: Animals; Brain; Rabies virus; Virulence
PubMed: 7859500
DOI: 10.1007/978-3-642-78490-3_5 -
PloS One 2017Near complete rabies virus N gene sequences (1,110 nt) were determined for 82 isolates obtained from different regions of Russia between 2008 and 2016. These sequences...
Near complete rabies virus N gene sequences (1,110 nt) were determined for 82 isolates obtained from different regions of Russia between 2008 and 2016. These sequences were analyzed together with 108 representative GenBank sequences from 1977-2016 using the Bayesian coalescent approach. The timing of the major evolutionary events was estimated. Most of the isolates represented the steppe rabies virus group C, which was found over a vast geographic region from Central Russia to Mongolia and split into three groups (C0-C2) with discrete geographic prevalence. A single strain of the steppe rabies virus lineage was isolated in the far eastern part of Russia (Primorsky Krai), likely as a result of a recent anthropogenic introduction. For the first time the polar rabies virus group A2, previously reported in Alaska, was described in the northern part of European Russia and at the Franz Josef Land. Phylogenetic analysis suggested that all currently circulating rabies virus groups in the Russian Federation were introduced within the few last centuries, with most of the groups spreading in the 20th century. The dating of evolutionary events was highly concordant with the historical epidemiological data.
Topics: Genome, Viral; Phylogeny; Rabies; Rabies virus; Russia
PubMed: 28225771
DOI: 10.1371/journal.pone.0171855