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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 -
Comparative Immunology, Microbiology... Jun 2023Rabies is a zoonotic disease caused by rabies virus of the genus Lyssa virus and family Rhabdoviridae. It affects all mammals and is prevalent throughout the world and... (Review)
Review
Rabies is a zoonotic disease caused by rabies virus of the genus Lyssa virus and family Rhabdoviridae. It affects all mammals and is prevalent throughout the world and endemic in many countries except in Islands like Australia and Antarctica. It is highly fatal, but preventable. Disease causes threat to public health because rabid dogs bite humans, resulting in thousands of deaths every year. Around 59,000 people die every year from rabies in the world. Dogs play a vital role in most of the human exposure in rabies endemic areas. Transmission of virus occurs through the bite of an infected dog. Disease is manifested by fatal nervous symptoms leading to paralysis and death. Direct fluorescent antibody technique is the gold standard for the diagnosis of the disease in animals and humans. Prevention of rabies involves the vaccination of dogs and humans before or after an exposure. This review describes the etiology, pathogenesis, diagnosis, its prevention and control strategies.
Topics: Animals; Dogs; Humans; Rabies; Public Health; Dog Diseases; Zoonoses; Rabies virus; Mammals; Bites and Stings; Rabies Vaccines
PubMed: 37229956
DOI: 10.1016/j.cimid.2023.101992 -
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 -
BMJ Case Reports Apr 2021Rabies is an almost always fatal disease that physicians and patients dread due to its dismal prognosis and limited treatment options. Transmission of this disease...
Rabies is an almost always fatal disease that physicians and patients dread due to its dismal prognosis and limited treatment options. Transmission of this disease occurs through the bite of dogs and wild animals (like jackal in our case). Other rare forms of transmission may be through inhalation in bat-infested caves and human-to-human transmission by infected corneal transplants, solid organ and tissue transplantation, and sometimes in laboratory settings. Its diagnosis is usually clinical in the absence of availability of special laboratory investigations at the point-of-care facility. Few people have described the role of imaging in diagnosis. We hereby report a patient with rabies encephalitis, having a history of jackal bite and classical MRI findings that we can use for early diagnosis in the absence of typical clinical features and specialised diagnostic testing.
Topics: Animals; Bites and Stings; Dogs; Encephalitis; Humans; Magnetic Resonance Imaging; Rabies; Rabies virus
PubMed: 33906884
DOI: 10.1136/bcr-2020-239249 -
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 -
Advances in Experimental Medicine and... 2023Lyssaviruses, which belong to the family Rhabdoviridae, are enveloped and bullet-shaped ssRNA viruses with genetic diversity. All members of Lyssavirus genus are known...
Lyssaviruses, which belong to the family Rhabdoviridae, are enveloped and bullet-shaped ssRNA viruses with genetic diversity. All members of Lyssavirus genus are known to infect warm-blooded animals and cause the fatal disease rabies. The rabies virus (RABV) in lyssavirus is the major pathogen to cause fatal rabies. The pseudotyped RABV is constructed to study the biological functions of G protein and evaluation of anti-RABV products including vaccine-induced antisera, rabies immunoglobulins (RIG), neutralizing mAbs, and other antiviral inhibitors. In this chapter, we focus on RABV as a representative and describe the construction of RABV G protein bearing pseudotyped virus and its applications. Other non-RABV lyssaviruses are also included.
Topics: Animals; Lyssavirus; Rabies; Viral Pseudotyping; Rhabdoviridae Infections; Rabies virus; Rabies Vaccines
PubMed: 36920698
DOI: 10.1007/978-981-99-0113-5_10 -
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 -
Viral Immunology Oct 2021Rabies is an almost invariably fatal disease. According to the World Health Organization (WHO), rabies virus neutralizing antibody (RVNA) titers of ≥0.5 IU/mL are... (Review)
Review
Rabies is an almost invariably fatal disease. According to the World Health Organization (WHO), rabies virus neutralizing antibody (RVNA) titers of ≥0.5 IU/mL are considered adequate for rabies protection. Therefore, detection and quantification of RABV antibodies are important. Many methods have been developed for detecting RABV antibodies. In the present study, we reviewed several methods of detecting RABV antibodies in human and animal samples and evaluated and compared their performance. Of 34 methods, 5 demonstrated unsatisfactory sensitivity or specificity. The others exhibited sensitivity and specificity of ≥75%. The correlation coefficient for five of eight methods was >0.8. The Bland-Altman mean bias of five of five methods was <±2.0. The kappa values of 25 of 28 methods were higher than 0.4, demonstrating at least moderate agreement. Analysis of the performance of these methods emphasized that any new technology should be considered carefully and objectively before being used as an appropriate and applicable alternative.
Topics: Animals; Antibodies, Neutralizing; Antibodies, Viral; Neutralization Tests; Rabies; Rabies virus
PubMed: 34550784
DOI: 10.1089/vim.2020.0317