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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 -
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 -
Animal Models and Experimental Medicine Oct 2022Rabies virus (RABV) is an infectious and neurotropic pathogen that causes rabies and infects humans and almost all warm-blooded animals, posing a great threat to people... (Review)
Review
Rabies virus (RABV) is an infectious and neurotropic pathogen that causes rabies and infects humans and almost all warm-blooded animals, posing a great threat to people and public safety. It is well known that innate immunity is the critical first line of host defense against viral infection. It monitors the invading pathogens by recognizing the pathogen-associated molecular patterns and danger-associated molecular patterns through pattern-recognition receptors, leading to the production of type I interferons (IFNα/β), inflammatory cytokines, and chemokines, or the activation of autophagy or apoptosis to inhibit virus replication. In the case of RABV, the innate immune response is usually triggered when the skin or muscle is bitten or scratched. However, RABV has evolved many ways to escape or even hijack innate immune response to complete its own replication and eventually invades the central nervous system (CNS). Once RABV reaches the CNS, it cannot be wiped out by the immune system or any drugs. Therefore, a better understanding of the interplay between RABV and innate immunity is necessary to develop effective strategies to combat its infection. Here, we review the innate immune responses induced by RABV and illustrate the antagonism mechanisms of RABV to provide new insights for the control of rabies.
Topics: Animals; Humans; Rabies virus; Rabies; Immunity, Innate; Cytokines; Chemokines
PubMed: 36138548
DOI: 10.1002/ame2.12273 -
Proceedings of the National Academy of... Jun 2019Mononegaviruses are promising tools as oncolytic vectors and transgene delivery vectors for gene therapy and regenerative medicine. By using the Magnet proteins, which...
Mononegaviruses are promising tools as oncolytic vectors and transgene delivery vectors for gene therapy and regenerative medicine. By using the Magnet proteins, which reversibly heterodimerize upon blue light illumination, photocontrollable mononegaviruses (measles and rabies viruses) were generated. The Magnet proteins were inserted into the flexible domain of viral polymerase, and viruses showed strong replication and oncolytic activities only when the viral polymerases were activated by blue light illumination.
Topics: Animals; Cell Line, Tumor; DNA-Directed RNA Polymerases; Genetic Therapy; Genetic Vectors; Humans; Light; Measles virus; Mice, Inbred BALB C; Mice, Nude; Oncolytic Virotherapy; Oncolytic Viruses; Rabies virus; Transgenes; Virus Replication
PubMed: 31138700
DOI: 10.1073/pnas.1906531116 -
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 -
Virology Journal Nov 2022Rabies is a lethal zoonotic disease that is mainly caused by the rabies virus (RABV). Although effective vaccines have long existed, current vaccines take both time and...
Rabies is a lethal zoonotic disease that is mainly caused by the rabies virus (RABV). Although effective vaccines have long existed, current vaccines take both time and cost to produce. Messenger RNA (mRNA) technology is an emergent vaccine platform that supports rapid vaccine development on a large scale. Here, an optimized mRNA vaccine construct (LVRNA001) expressing rabies virus glycoprotein (RABV-G) was developed in vitro and then evaluated in vivo for its immunogenicity and protective capacity in mice and dogs. LVRNA001 induced neutralizing antibody production and a strong Th1 cellular immune response in mice. In both mice and dogs, LVRNA001 provided protection against challenge with 50-fold lethal dose 50 (LD) of RABV. With regards to protective efficiency, an extended dosing interval (14 days) induced greater antibody production than 3- or 7-day intervals in mice. Finally, post-exposure immunization against RABV was performed to evaluate the survival rates of dogs receiving two 25 μg doses of LVRNA001 vs. five doses of inactivated vaccine over the course of three months. Survival rate in the LVRNA001 group was 100%, whereas survival rate in the inactivated vaccine control group was only 33.33%. In conclusion, these results demonstrated that LVRNA001 induced strong protective immune responses in mice and dogs, which provides a new and promising prophylactic strategy for rabies.
Topics: Dogs; Mice; Animals; Rabies Vaccines; Rabies; RNA, Messenger; Antibodies, Viral; Rabies virus; Vaccines, Inactivated; Antibody Formation; mRNA Vaccines
PubMed: 36371169
DOI: 10.1186/s12985-022-01919-7 -
Cells Jan 2024Rabies virus (RABV) is a single-stranded negative-sense RNA virus belonging to the family and genus, which is highly neurotropic and can infect almost all warm-blooded... (Review)
Review
Rabies virus (RABV) is a single-stranded negative-sense RNA virus belonging to the family and genus, which is highly neurotropic and can infect almost all warm-blooded animals, including humans. Autophagy and apoptosis are two evolutionarily conserved and genetically regulated processes that maintain cellular and organismal homeostasis, respectively. Autophagy recycles unnecessary or dysfunctional intracellular organelles and molecules in a cell, whereas apoptosis eliminates damaged or unwanted cells in an organism. Studies have shown that RABV can induce both autophagy and apoptosis in target cells. To advance our understanding of pathogenesis of rabies, this paper reviews the molecular mechanisms of autophagy and apoptosis induced by RABV and the effects of the two cellular events on RABV replication.
Topics: Animals; Humans; Rabies virus; Rabies; Apoptosis; Autophagy; Virus Replication
PubMed: 38247875
DOI: 10.3390/cells13020183 -
Virologica Sinica Aug 2021Rabies is caused by infection of rabies virus (RABV) and remains a serious threat to the global public health. Except for the requirement for cold chain and high cost...
Rabies is caused by infection of rabies virus (RABV) and remains a serious threat to the global public health. Except for the requirement for cold chain and high cost of human rabies immune globulin, no small molecule drugs are currently available for clinical treatment of rabies. So, it is of great importance to identify novel compounds that can effectively inhibit RABV infection. Artesunate (ART) and dihydroartemisinin (DHA), two derivatives of artemisinin, are widely used for treatment of malaria in adults and children, showing high safety. In this study, we found that both ART and DHA were able to inhibit RABV replication in host cells at a low concentration (0.1 μmol/L). The antiviral effects of ART and DHA were independent of viral strains and cell lines. Pre-treatment with ART or DHA for 2 h in vitro did not affect the viral replication in host cells, implying that ART and DHA neither reduced the viability of RABV directly nor inhibited the binding and entrance of the virus to host cells. Further studies revealed that ART and DHA inhibited RABV genomic RNA synthesis and viral gene transcription. Treatment with ART or DHA (5 mg/kg) by intramuscular injection improved, to some extent, the survival rate of RABV-challenged mice. Combination treatment with derivatives of artemisinin and mannitol significantly improved the survival rate of RABV-challenged mice. The results suggest that ART and DHA have a great potential to be explored as new anti-rabies agents for treatment of rabies.
Topics: Animals; Artemisinins; Artesunate; Mice; Rabies; Rabies virus; Virus Replication
PubMed: 33661488
DOI: 10.1007/s12250-021-00349-z -
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