Materiały źródłowe

• #1 Rabies | Nature Reviews Disease Primers

  https://www.nature.com/articles/nrdp201791

  Rabies is a life-threatening neglected tropical disease: tens of thousands of cases are reported annually in endemic countries (mainly in Africa and Asia), although the actual numbers are most likely underestimated. […] The virus first infects peripheral motor neurons, and symptoms occur after the virus reaches the central nervous system. Once clinical disease develops, it is almost certainly fatal. […] A multifaceted approach for human rabies eradication that involves government support, disease awareness, vaccination of at-risk human populations and, most importantly, dog rabies control is necessary to achieve the WHO goal of reducing the number of cases of dog-mediated human rabies to zero by 2030. […] Jackson, A. C. Rabies pathogenesis. […] Hemachudha, T. et al. Human rabies: neuropathogenesis, diagnosis, and management.

• #1 Rabies virus – Wikipedia

  https://en.wikipedia.org/wiki/Rabies_virus

  Rabies virus (Lyssavirus rabies) is a neurotropic virus that causes rabies in animals, including humans. […] Rabies virus has a cylindrical morphology and is a member of the Lyssavirus genus of the Rhabdoviridae family. These viruses are enveloped and have a single stranded RNA genome with negative-sense. […] All transcription and replication events take place in the cytoplasm inside a specialized „virus factory”, the Negri body. […] The next step after its entry is the transcription of the viral genome by the P-L polymerase (P is an essential cofactor for the L polymerase) in order to make new viral protein. […] The retrograde axonal transport of Rabies virus to the central nervous system (CNS) is the key step of pathogenesis during natural infection. […] P also acts as an interferon antagonist, thus decreasing the immune response of the host. […] The interactions between the L protein and the M protein have also been noted to be of importance to its function. […] The polymerase is an enzyme and can aid in initiation, elongation, capping, methylation, polyadenylation and RNA polymerization.

• #1 Rabies – Wikipedia

  https://en.wikipedia.org/wiki/Rabies

  Rabies is caused by lyssaviruses, including the rabies virus and Australian bat lyssavirus. […] The rabies virus is the type species of the Lyssavirus genus, in the family Rhabdoviridae, order Mononegavirales. Lyssavirions have helical symmetry, with a length of about 180 nm and a cross-section of about 75 nm. […] To enter cells, trimeric spikes on the exterior of the membrane of the virus interact with a specific cell receptor, the most likely one being the acetylcholine receptor. The cellular membrane pinches in a procession known as pinocytosis and allows entry of the virus into the cell by way of an endosome. The virus then uses the acidic environment, which is necessary, of that endosome and binds to its membrane simultaneously, releasing its five proteins and single-strand RNA into the cytoplasm.

• #1 Transmission and pathogenesis | Rabies – Bulletin – Europe

  https://www.who-rabies-bulletin.org/site-page/transmission-and-pathogenesis

  In most cases the disease is transmitted via the bite of rabid animals which shed infectious virus with their saliva. The virus enters the body through transdermal inoculation (i.e. wounds) or direct contact of infectious material (i.e. saliva, cerebrospinal liquid, nerve tissue) to mucous membranes or skin lesions. The virus can not penetrate intact skin. […] After entry the virus binds to cell receptors. Viruses may replicate within striated muscle cells ore directly infect nerve cells. […] The virus then travels via retrograde axoplasmatic transport mechanisms to the central nervous system. Both motor and sensory fibres may be involved depending on the animal infected. […] Once it has reached the CNS, rapid virus replication takes place, causing pathologic effects on nerve cell physiology. The virus then moves from the CNS via anterograde axoplasmic flow within peripheral nerves, leading to infection of some of the adjacent non-nervous tissues, for example, secretory tissues of salivary glands. The virus is widely disseminated throughout the body at the time of clinical onset. With shedding of infectious virus in saliva the infection cycle of rabies is completed.

• #1 Rhabdoviruses: Rabies Virus – Medical Microbiology – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK8618/

  Rabies virus causes acute infection of the central nervous system. […] After inoculation, rabies virus may enter the peripheral nervous system directly and migrates to the brain or may replicate in muscle tissue, remaining sequestered at or near the entry site during incubation, prior to central nervous system invasion and replication. It then spreads centrifugally to numerous other organs. The case:fatality ratio approaches unity, but exact pathogenic mechanisms are not fully understood. […] Rabies virus is most commonly transmitted through the bite of an infected mammal, all of which may be susceptible, but to greatly varying degrees. The virus may enter the peripheral nervous system directly, or may replicate in muscle tissue after entering the host, remaining at or near the site of introduction for most of the incubation period. However, the precise sites of viral sequestration remain unknown, since neither antigen nor virus can usually be found in any organ during this phase.

• #1 Rabies | Nature Reviews Disease Primers

  https://www.nature.com/articles/nrdp201791

  The data in this paper show that the production of rabies-virus-specific antibodies by infiltrating B cells across the bloodbrain barrier is crucial for the elimination of rabies virus. […] The data in this paper indicate that acetylcholine receptors serve as receptors for the rabies virus. […] The data in this paper show that the rabies virus phosphoprotein is responsible for preventing IFN-/-stimulated and IFN–stimulated JAK-STAT signalling in rabies-virus-infected cells by the retention of activated STATs (signal transducer and activator of transcription) in the cytoplasm. […] The data in this paper show that the rabies virus phosphoprotein is an interferon antagonist counteracting transcriptional activation of type I interferon.

• #1 Rabies Virus- An Overview

  https://microbenotes.com/rabies-virus/

  After inoculation of infectious saliva by bite, virus may persist and replicate in muscle tissue before progressing to the peripheral nervous tissue via neuromuscular junction. […] Neurotropsim is a main feature associated with viral replication residing exclusively to neurons. […] A significant interaction of G protein and acetylcholine receptor provide evidence of viral attachment. […] After peripheral nerve entry, virus moves centripetally within axons to the CNS via transportation by retrograde axonal flow. […] Incubation period is dependent on the distance between site of bite and CNS. […] Apart from this, it also depends on age of host, immune status of host, viral strain involved and amount of inoculation. […] In the CNS, the multiplication of the virus occurs in the grey matter and spreads in the endoneurium of Schwann cell. […] Virus spread may be facilitated by movement across cell to cell junctions. […] After period of multiplication, it disseminate into tissues and organs via efferent neurons.

• #1 Real-time Imaging of Rabies Virus Entry into Living Vero cells | Scientific Reports

  https://www.nature.com/articles/srep11753

  Understanding the mechanism of virus infection is vital for therapy of viral diseases. […] It has been established that rabies virus enter the host cell via receptor-mediated endocytosis and subsequent low pH-dependent fusion and the endocytic pathway is proven to be clathrin-mediated. […] Here, we employed live SRV9 as the surrogate of wild-type RABV to comprehensively evaluate the endocytosis pathway. […] Together, these results indicate that dynamin-dependent and clathrin-mediated endocytosis is involved SRV9 entry. […] Our results intuitively disclosed that SRV9 was internalized into Vero cells by a clathrin-dependent and actin-dependent pathway similar with VSV, IHNV and ABLV. […] The data presented in this study suggest that RABV internalization into host cells occurs through a dynamin-dependent CME pathway, rather than caveolae-dependent.

• #1 Rabies Virus Hijacks and Accelerates the p75NTR Retrograde Axonal Transport Machinery | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004348

  Rabies virus (RABV) is a neurotropic virus that depends on long distance axonal transport in order to reach the central nervous system (CNS). […] The strategy RABV uses to hijack the cellular transport machinery is still not clear. […] Here we used live cell imaging to track RABV entry at nerve terminals and studied its retrograde transport along the axon with and without the p75NTR receptor. […] RABV and NGF were internalized at similar time frames, suggesting comparable entry machineries. […] Interestingly, RABV is transported faster than NGF, suggesting that RABV not only hijacks the transport machinery but can also manipulate it. […] Finally, we determined that p75NTR-dependent transport of RABV is faster and more directed than p75NTR-independent RABV transport. […] Hence, RABV may employ p75NTR-dependent transport as a fast mechanism to facilitate movement to the CNS.

• #1 Pathogenesis of Rabies | SpringerLink

  https://link.springer.com/chapter/10.1007/3-540-27485-5_3

  Rabies is a central nervous system (CNS) disease that is almost invariably fatal. The causative agent is rabies virus (RV), a negative-stranded RNA virus of the rhabdovirus family. RV pathogenesis, like that of other viruses, is a multigenic trait. Recent findings indicate that in addition to the RV G protein viral elements that regulate gene expression, especially expression of the L gene, are also likely to play a role in RV pathogenesis. […] In vivo, RV infects almost exclusively neurons, and neuroinvasiveness is the major defining characteristic of a classical RV infection. A key factor in the neuroinvasion of RV is transsynaptic neuronal spread. While the ability of RV to spread from the post-synaptic site to the pre-synaptic site is mediated by the RV G protein, the RV P protein might be an important determinant of retrograde transport of the virus within axons.

• #1 Rabies Virus: Structure, Pathogenesis, and Lab Diagnosis • Microbe Online

  https://microbeonline.com/virology-note-rabies-virus-structure-pathogenesis-and-clinical-findings/

  Rabies virus multiplies in muscle or connective tissues at the site of inoculation for 48 to 72 hrs enters peripheral nerves at neuromuscular junction spreads up the nerves to CNS multiplies in the CNS and progressive encephalitis develops and spreads centrifugally along the peripheral nerve trunk to various body parts including the salivary glands where it multiplies and is shed in saliva; organ with the highest titer of a virus is a submaxillary gland. […] The virus produces a specific eosinophilic cytoplasmic inclusion, the Negri body in infected nerve cells, which are round or oval, purplish-pink structure and varies in size from 3-27 m; the Negri bodies are filled with viral nucleocapsids. […] The pathogenicity of a strain is related to its capacity to induce cell fusion in neuroblastoma cells. Observable damage to nerve cells in the brain appears minimal; non-specific changes include parenchymal microglial response and perivascular cuffing, with lymphocyte and plasma cell infiltration in the grey matter of the brain stem and spinal cord.

• #1 Rhabdoviruses: Rabies Virus – Medical Microbiology – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK8618/

  Virus may enter the peripheral nervous system via the neuromuscular junctions, and moves rapidly centripetally to the central nervous system for replication; symptoms may develop shortly thereafter. The virus then begins to pass centrifugally to many tissues and organs, such as the salivary glands. […] In general, gross examination of the brain shows mild congestion of the meningeal vessels; microscopic examination usually demonstrates slight perivascular cuffing, limited tissue necrosis, acidophilic intracytoplasmic neuronal inclusions, and rarely, neuronophagia.

• #1 VIROLOGY – RABIES VIRUS | PPT

  https://www.slideshare.net/slideshow/virology-rabies-virus/251712476

  Rabies virus multiplies in muscle or connective tissue at the site of inoculation Then enters peripheral nerves at neuromuscular junctions and spreads up the nerves to the central nervous system. […] However, it is also possible for rabies virus to enter the nervous system directly without local replication. It multiplies in the central nervous system and progressive encephalitis develops. The virus then spreads through peripheral nerves to the salivary glands and other tissues. The organ with the highest titers of virus is the submaxillary salivary gland. Other organs where rabies virus has been found include pancreas, kidney, heart, retina, and cornea. Rabies virus has not been isolated from the blood of infected persons. […] Rabies infection usually results from the bite of rabid dogs or other animals. The virus present in the saliva of the animal is deposited in the wound. The virus appears to multiply in the muscles, connective tissue or nerves at the site of deposition. The virus remains at the site for days to months before progressing to the central nervous system (CNS). Rabies virus travels by retrograde axoplasmic transport to the dorsal root ganglia and to the spinal cord. Once the virus gains access to the spinal cord, the brain becomes rapidly infected. The virus then disseminates from the CNS via afferent neurons to highly innervated sites, such as the skin of the head and neck, salivary glands, retina, cornea, nasal mucosa etc. The virus ultimately reaches virtually every tissue in the body, though the centrifugal dissemination may be interrupted at any stage by death. Rabies is fatal once clinical disease is apparent.

• #1 VIROLOGY – RABIES VIRUS | PPT

  https://www.slideshare.net/slideshow/virology-rabies-virus/251712476

  Susceptibility to infection and the incubation period may depend upon Host’s age Genetic background Immune status Viral strain involved Amount of inoculum The severity of lacerations The distance the virus has to travel from its point of entry to the central nervous system. There is a higher attack rate and shorter incubation period in persons bitten on the face or head; the lowest mortality occurs in those bitten on the legs.

• #1

  https://www.who-rabies-bulletin.org/member/About_Rabies/Transmission_Pathogenesis.aspx

  In most cases the disease is transmitted via the bite of rabid animals which shed infectious virus with their saliva. The virus enters the body through transdermal inoculation (i.e. wounds) or direct contact of infectious material (i.e. saliva, cerebrospinal liquid, nerve tissue) to mucous membranes or skin lesions. The virus cannot penetrate intact skin. […] After entry the virus binds to cell receptors. Viruses may replicate within striated muscle cells or directly infect nerve cells. […] The virus then travels via retrograde axoplasmatic transport mechanisms to the central nervous system. Both motor and sensory fibres may be involved depending on the animal infected. The incubation period varies from 2 weeks to 6 years (average 23 months) depending on the amount of virus in the saliva, the site of inoculation and the virus strain.

• #1 Rabies in Animals – Nervous System – MSD Veterinary Manual

  https://www.msdvetmanual.com/nervous-system/rabies/rabies-in-animals

  The incubation period of rabies is both prolonged and variable, depending on the exposure site and dose of viral inoculum. […] The unusual length of the incubation period helps to explain the effective action of local infiltration of rabies immune globulin during human postexposure prophylaxis, even days after exposure. […] The clinical course of rabies may be divided into three general phases prodromal, acute excitative, and paralytic (end stage). […] The disease progresses swiftly after the onset of paralysis, and death is virtually certain a few days thereafter. […] The paralysis progresses rapidly to all parts of the body, and coma and death follow in a few hours. […] Rabies vaccination and registration of cats and dogs […] Integrated veterinary management of local animal populations, by mass vaccination of dogs and community promotion of responsible pet ownership, is the most cost-effective, humane, longterm solution to eliminating regional rabies virus variants in a One Health context. […] As an enveloped virus, rabies virus is inactivated by various disinfectants (eg, formalin, phenol, alcohol, halogens, mercurials, mineral acids).

• #1 Rabies: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/220967-overview

  Rabies virus infection is remarkable for the lack of evident pathology despite dramatic neurologic symptoms. Minimal inflammation and neuronal cytopathy may be observed even postmortem. Similarly, viremia does not occur or play a role in spread to the CNS. […] Pathophysiology has been best characterized in canine rabies variants. Canine rabies in humans requires deep-muscle inoculation. Endogenous muscle micro-RNA bind to viral transcripts and limit both replication and viral protein production, such that the virus is able to evade detection by antigen-presenting cells. Once enough virus replicates (or with a high-level inoculum or direct nerve injury), it binds motor neuron junctions at postsynaptic nicotinic acetylcholine receptors, which initiates uptake into the motor endplate. From here, the virus rapidly propagates across motor axons and chemical synapses in retrograde fashion toward the ganglia and nerve roots, at which point the prodromal symptoms of neuralgia and hypoesthesia may begin, in addition to fever and flulike illness.

• #1 Multi-Omics in Rabies Virus Infection – Creative Proteomics

  https://www.creative-proteomics.com/viromics/multi-omics-in-rabies-virus-infection.htm

  Rabies is an invariably fatal neurological disease, which seriously threatens human and animal health. […] a thorough understanding of rabies virus (RABV) pathogenesis is necessary. […] the pathogenesis of RABV, such as identifying links between viral genome characteristics and clinical manifestations of disease can be addressed using genomic approaches. […] Transcriptome studies have found that there are two major mechanisms of RABV pathogenesis, including immune responses and alteration of neuronal homeostasis. […] RABV infection leads to dysregulation of cytoskeletal and structural proteins, thus resulting in impaired integrity and cellular structure. […] RABV-induced autophagy has been suggested as another mechanism of neuronal pathology. […] the relationship between PTM of host proteins and the pathogenesis of RABV requires further study.

• #1 Rabies | MedLink Neurology

  https://www.medlink.com/articles/rabies

  Rabies virus disseminates rapidly within the CNS by fast axonal transport, and widespread infection of neurons with selectivity occurs. […] Subsequently, the virus spreads along neural pathways to multiple organs (centrifugal spread), including the salivary glands, adrenal medulla, heart, and skin. […] The basis of the neuronal dysfunction in rabies is unknown. […] Experimental studies in mice after peripheral inoculation have shown that structural abnormalities in neuronal processes may explain the fatal clinical disease in rabies, which may be due to oxidative stress related, at least in part, to mitochondrial dysfunction due to interaction of the rabies virus phosphoprotein with mitochondrial complex I. […] There is also evidence of mitochondrial dysfunction in naturally infected dog and human brains. […] Hydrophobia is likely due to selective infection of neurons that inhibit brainstem neurons near nucleus ambiguus, resulting in exaggeration of defense reflexes that normally protect the respiratory tract.

• #1 The Immune Escape Strategy of Rabies Virus and Its Pathogenicity Mechanisms

  https://www.mdpi.com/1999-4915/16/11/1774

  The Immune Escape Strategy of Rabies Virus and Its Pathogenicity Mechanisms […] In contrast to most other rhabdoviruses, which spread by insect vectors, the rabies virus (RABV) is a very unusual member of the Rhabdoviridae family, since it has evolved to be fully adapted to warm-blooded hosts and spread directly between them. […] Pathogenic RABV infection bypasses immune response by antagonizing interferon induction, which prevents downstream signal activation and impairs antiviral proteins and inflammatory cytokines production that could eliminate the virus. […] Furthermore, early apoptosis of neural cells limit replication and spread of avirulent RABV infection, but street RABV strains infection cause delayed apoptosis that help them spread further to healthy cells and circumvent early immune exposure. […] Infection with laboratory fixed RABV strains lead to complete autophagy and the viruses are eliminated. But incomplete autophagy during pathogenic RABV infection failed to destroy the viruses and might aid the virus in dodging detection by antigen-presenting cells, which could otherwise elicit adaptive immune activation. […] Pathogenic RABV P and M proteins, as well as high concentration of nitric oxide, which is produced during rabies virus infection, inhibits activities of mitochondrial proteins, which triggers the generation of reactive oxygen species, resulting in oxidative stress, contributing to mitochondrial malfunction and, finally, neuron process degeneration. […] The RABV P protein is a multifunctional antagonist which can block the activation of immune-stimulatory and antiviral genes. […] The RABV p protein and M protein inhibit mitochondrial complex I and cytochrome c oxidase activity, respectively. High concentrations of NO during RABV infection compete with oxygen for cytochrome c oxidase. […] The outcome of a wild-type RABV infection in the CNS depends on the degree of infection and whether immune clearance results in significant neuron loss. […] The study also discovered that an adaptive immune response using CD4 T cells is crucial for managing the infection, and F11’s ability to bind FcRc improves treatment effectiveness. […] This review recaps the current understanding of rabies and provides an insight into its subversive strategy to bypass the immune response and pathogenicity mechanisms of several RABV strains.

• #1 Pathogenesis of Rabies | SpringerLink

  https://link.springer.com/chapter/10.1007/3-540-27485-5_3

  Although the mechanism(s) by which an RV infection cause(s) a lethal neurological disease are still not well understood, the most significant factor underlying the lethal outcome of an RV infection appears to be the neuronal dysfunction due to drastically inhibited synthesis of proteins required in maintaining neuronal functions.

• #1 SciELO Brazil – Rabies review: immunopathology, clinical aspects and treatment Rabies review: immunopathology, clinical aspects and treatment

  https://www.scielo.br/j/jvatitd/a/PZMf65MHTJjpRdsNT9Z6Hxw/

  Among the diseases of viral origin, rabies is unique in its distribution and range of victims since it can afflict all warm-blooded animals. […] Infection by RV is invariably lethal in the absence of protective immune response which, however, can contribute to the pathogenesis of rabies. […] Although understanding of the bases for neuronal dysfunction and neuronal death during RV infection has progressed, no fundamental abnormality has been identified so far. […] One of the most surprising aspects of rabies immunopathology is the almost complete lack of an inflammatory response within the CNS characterized by perivascular cuffing with mononuclear cells, local gliosis and neuronophagia. […] These observations suggest that neuronal dysfunction, rather than neuronal death, is probably responsible for the fatal outcome of rabies under normal conditions.

• #1 SciELO Brazil – Rabies review: immunopathology, clinical aspects and treatment Rabies review: immunopathology, clinical aspects and treatment

  https://www.scielo.br/j/jvatitd/a/PZMf65MHTJjpRdsNT9Z6Hxw/

  The cause of functional alterations in RV-infected neurons is not clear yet. […] Apoptosis is induced via both virus-dependent and cell-dependent mechanisms. […] Thus, preservation of the neurons and limitation of such network by inhibiting apoptosis and limiting inflammation and destruction of T cells that invade the CNS in response to the infection is crucial for the RV neuroinvasion and transmission to another animal.

• #1 Azthena logo with the word Azthena

  https://www.news-medical.net/health/Why-is-the-Rabies-CFR-So-High.aspx

  The virus exploits the blood-brain barrier (BBB) to achieve self-protection. […] With the rabies virus, however, the blood-brain barrier remains impermeable despite the entry of the virus, perhaps because the virus has the ability to prevent inflammation and the resulting release of cytokines and chemokines. […] The mechanism by which this is achieved remains unknown but could be highly promising in its potential for the management of rabies. […] Neuroinvasiveness, neurotropism, and neurovirulence are the major defining characteristics of RV (rabies virus). […] To infect the CNS, pathogenic street RVs have acquired the ability for rapid entry and efficient spread, while producing only low amounts of viral RNA and proteins in order to prevent cell injury.

• #1 How does rabies cause aggression?

  https://www.medicalnewstoday.com/articles/319735

  Our study provides, for the first time, a detailed molecular mechanism for how an infectious agent induces specific behaviors. […] That research showed how glycoprotein molecules of the virus bind to acetylcholine receptor molecules, which, in addition to influencing the signaling pathway that dictates muscle control, means that they can also replicate and infect the brain. […] Dr. Hueffer and colleague Dr. Marvin Schulte who specializes in nicotine receptors connected the dots between these existing findings, and they saw that the properties of amino acids in rabies glycoprotein might be key in influencing the hosts frenzied behavior following infection with the virus. […] If snake venom has a similar structure to parts of the virus, and inhibits these receptors, we thought maybe the virus could also inhibit these receptors in the brain. Furthermore, we thought that this interaction could influence behavior. […] According to Dr. Hueffer and his team, this is the first time that experimental evidence has been presented to show how rabies interacts with other cells in the nervous system to induce an altered behavior that determines infected hosts to help spread the virus.

• #1 Concepts in the Pathogenesis of Rabies

  https://www.medscape.com/viewarticle/581903_0

  RV G is the major determinant of the pathogenesis of rabies. […] RV G facilitates fast virus entry and fast trans-synaptic spread and regulates the rate of virus replication together with other viral elements. […] The pathogenicity of RV correlates inversely with its capacity to induce neuronal apoptosis. […] There is a direct correlation between RV G expression level and extent of apoptosis. […] In contrast with attenuated RVs, pathogenic street RVs express very limited levels of G protein and do not induce apoptosis or necrosis. […] Weaker activation of NF-B pathway-related genes and consequently a weaker immune response induced by pathogenic RVs might allow the spread of the virus to the CNS.

• #1 Rabies – Neurologic Disorders – MSD Manual Professional Edition

  https://www.msdmanuals.com/professional/neurologic-disorders/brain-infections/rabies

  After exposure to an animal who has or is suspected of having rabies, thoroughly clean and debride any wounds, then give the rabies vaccine and rabies immune globulin. […] Raccoons, skunks, or foxes that have bitten a person should be regarded as rabid; because bat bites can be minute and hard to detect, contact with a bat is an absolute indication for rabies immune globulin and the rabies vaccine.

• #1 Rabies: Symptoms, causes, vaccine, treatment, and prevention

  https://www.medicalnewstoday.com/articles/181980

  A person may enter a coma, and most people then die within 2 to 3 days. During the coma stage, even with supportive therapy, virtually no person survives rabies. […] If a person has a bite or scratch from an animal that may have rabies, or if the animal licks an open wound, the individual should immediately wash any bites and scratches for 15 minutes with soapy water, povidone iodine, or detergent. This might minimize the number of viral particles. […] After exposure and before symptoms begin, a series of injections can treat potential rabies infections. […] Rabies vaccine contains an inactivated or a harmless version of the rabies virus, so it cannot cause the disease. It triggers the immune response to produce antibodies, which remain in the body and help protect against future rabies infections. […] For postexposure protection, previously unvaccinated people need four doses of the rabies vaccine, plus rabies immune globulin (RIG).

• #1 What is the mechanism of Rabies Vaccine Adsorbed?

  https://synapse.patsnap.com/article/what-is-the-mechanism-of-rabies-vaccine-adsorbed

  1. Antigen Presentation: The inactivated rabies virus particles in the vaccine are recognized as foreign by the body’s immune system. Antigen-presenting cells (APCs), such as dendritic cells and macrophages, engulf these virus particles and process them. The APCs then present the viral antigens on their surfaces using molecules known as major histocompatibility complex (MHC) proteins. […] 2. Activation of T Cells: The presented antigens on APCs are recognized by T cells, a type of white blood cell that plays a central role in the immune response. This recognition stimulates the activation and proliferation of helper T cells (CD4+ T cells). […] 3. B Cell Activation and Antibody Production: The helper T cells, in turn, assist in activating B cells, another type of white blood cell. Once activated, B cells differentiate into plasma cells that produce antibodies specifically targeted against the rabies virus antigens. These antibodies are proteins that can neutralize the virus, preventing it from infecting cells.

• #1 Rabies: Causes, Symptoms, Treatment & Prevention

  https://my.clevelandclinic.org/health/diseases/13848-rabies

  Rabies is preventable. Keeping your pets safe and staying away from wild animals will help prevent you from being exposed to rabies. If you’re exposed, you can get a vaccine to prevent rabies before symptoms start. […] Theres no cure for rabies once its moved to your brain because its protected by your blood-brain barrier. […] Researchers arent sure how, but rabies locks this barrier down even further, so medications that might destroy it cant get through.

• #1 Rabies | Yellow Book | CDC

  https://wwwnc.cdc.gov/travel/yellowbook/2024/infections-diseases/rabies

  Once clinical signs appear, patients die quickly in the absence of intensive supportive care. […] Definitive antemortem diagnosis requires use of specialized diagnostic methods on multiple specimens, including cerebrospinal fluid (CSF), saliva, serum, and skin biopsies taken from the nape of the neck. […] Finding rabies virus antigen or nucleic acid in any antemortem sample confirms the diagnosis. […] Rabies is a nationally notifiable disease. […] No evidence-based approach to treating rabies patients is available. […] Survival after the clinical phase of rabies virus infection is incredibly rare, but case reports continue to provide insight into potential therapeutic options, and experimental treatment regimens continue to be investigated. […] Rabies is still considered universally fatal for practical purposes; avoiding rabies virus exposures remains the most important prevention measure.

• #1 Natural Infection with Rabies Virus: A Histopathological and Immunohistochemical Study of Human Brains

  https://ophrp.org/journal/view.php?doi=10.24171/j.phrp.2019.10.1.03

  Objectives Despite all the efforts and increased knowledge of rabies, the exact mechanisms of infection and mortality from the rabies virus are not well understood. […] However, the exact mechanisms underlying RV infection in human and the pathogenesis of rabies are not completely understood. […] To develop an effective therapeutic approach, it is important to fully understand the mechanism by which rabies causes lethal neurological disease. […] Due to the neurotropic nature of RV infection, understanding rabies pathogenesis requires knowledge of histopathological and immunohistochemical characteristics of the disease in the CNS. […] For a precise understanding of the mechanisms underlying the pathogenicity of RV infection, it is crucial to study tissue from infected humans. […] The results observed in this study through detailed histology of human cerebellum following infection with wild-type street rabies, showed insight into the immunology behind the infection indicating innate immunity may aggravate disease progression.

• #2 Concepts in the pathogenesis of rabies

  https://pmc.ncbi.nlm.nih.gov/articles/PMC2600441/

  Rabies is a zoonotic disease that remains an important public health problem worldwide and causes more than 70,000 human deaths each year. Neuroinvasiveness and neurotropism are the main features that define the pathogenesis of rabies. Although RV pathogenicity is a multigenic trait involving several elements of the RV genome, the RV glycoprotein plays a major role in RV pathogenesis by controlling the rate of virus uptake and trans-synaptic virus spread, and by regulating the rate of virus replication. The high neuroinvasiveness of pathogenic street RVs is, at least in part, due to their ability to evade immune responses and to conserve the structures of neurons. The key factors involved in neuroinvasion by RV are virus uptake, axonal transport, trans-synaptic spread and the rate of virus replication. The pathogenic mechanism that might contribute to the profound CNS dysfunction, characteristic of rabies, could be the impairment of neuronal functions. The pathogenicity of RV correlates inversely with its capacity to induce neuronal apoptosis. The expression level of RV G correlates directly with the extent of neuronal apoptosis, inflammatory lesions in the CNS and anti-RV immunity, but inversely with the pathogenicity of the RV. Pathogenicity correlates directly with the kinetics of virus uptake and virus spread, but inversely with the rate of virus replication and the expression level of RV G. The mechanisms by which RV G mediates neuroinvasion include the facilitation of fast virus entry and fast trans-synaptic spread, and regulation of viral RNA synthesis.

• #2 Rabies Virus: Structure, Pathogenesis, and Lab Diagnosis • Microbe Online

  https://microbeonline.com/virology-note-rabies-virus-structure-pathogenesis-and-clinical-findings/

  Rabies virus multiplies in muscle or connective tissues at the site of inoculation for 48 to 72 hrs enters peripheral nerves at neuromuscular junction spreads up the nerves to CNS multiplies in the CNS and progressive encephalitis develops and spreads centrifugally along the peripheral nerve trunk to various body parts including the salivary glands where it multiplies and is shed in saliva; organ with the highest titer of a virus is a submaxillary gland. […] The virus produces a specific eosinophilic cytoplasmic inclusion, the Negri body in infected nerve cells, which are round or oval, purplish-pink structure and varies in size from 3-27 m; the Negri bodies are filled with viral nucleocapsids. […] The pathogenicity of a strain is related to its capacity to induce cell fusion in neuroblastoma cells. Observable damage to nerve cells in the brain appears minimal; non-specific changes include parenchymal microglial response and perivascular cuffing, with lymphocyte and plasma cell infiltration in the grey matter of the brain stem and spinal cord.

• #2

  https://www.who-rabies-bulletin.org/member/About_Rabies/Transmission_Pathogenesis.aspx

  In most cases the disease is transmitted via the bite of rabid animals which shed infectious virus with their saliva. The virus enters the body through transdermal inoculation (i.e. wounds) or direct contact of infectious material (i.e. saliva, cerebrospinal liquid, nerve tissue) to mucous membranes or skin lesions. The virus cannot penetrate intact skin. […] After entry the virus binds to cell receptors. Viruses may replicate within striated muscle cells or directly infect nerve cells. […] The virus then travels via retrograde axoplasmatic transport mechanisms to the central nervous system. Both motor and sensory fibres may be involved depending on the animal infected. The incubation period varies from 2 weeks to 6 years (average 23 months) depending on the amount of virus in the saliva, the site of inoculation and the virus strain.

• #2 Rabies: Symptoms, causes, vaccine, treatment, and prevention

  https://www.medicalnewstoday.com/articles/181980

  Rabies is a viral infection that primarily spreads through a bite from an infected animal. Without early treatment, it is usually fatal. […] It is an RNA virus of the rhabdovirus family that can affect the body in one of two ways. It can enter the peripheral nervous system directly and migrate to the brain. It can also replicate within muscle tissue, where it is safe from the hosts immune system. From here, it enters the nervous system through the neuromuscular junctions. […] Once inside the nervous system, the virus produces acute inflammation of the brain. Coma and death soon follow. […] Rabies progresses in five distinct stages: incubation, prodrome, acute neurologic period, coma, and death. […] During this stage, neurologic symptoms develop, including confusion and aggression, partial paralysis, involuntary muscle twitching, rigid neck muscles, convulsions, hyperventilation and difficulty breathing, hypersalivation, or producing a lot of saliva, frothing at the mouth, fear of water, or hydrophobia, hallucinations, nightmares, and insomnia.

• #2 Rabies: Practice Essentials, Background, Etiology

  https://emedicine.medscape.com/article/220967-overview

  Rabies virus infection is remarkable for the lack of evident pathology despite dramatic neurologic symptoms. Minimal inflammation and neuronal cytopathy may be observed even postmortem. Similarly, viremia does not occur or play a role in spread to the CNS. […] Pathophysiology has been best characterized in canine rabies variants. Canine rabies in humans requires deep-muscle inoculation. Endogenous muscle micro-RNA bind to viral transcripts and limit both replication and viral protein production, such that the virus is able to evade detection by antigen-presenting cells. Once enough virus replicates (or with a high-level inoculum or direct nerve injury), it binds motor neuron junctions at postsynaptic nicotinic acetylcholine receptors, which initiates uptake into the motor endplate. From here, the virus rapidly propagates across motor axons and chemical synapses in retrograde fashion toward the ganglia and nerve roots, at which point the prodromal symptoms of neuralgia and hypoesthesia may begin, in addition to fever and flulike illness.

• #2 Rabies | Yellow Book | CDC

  https://www.cdc.gov/yellow-book/hcp/travel-associated-infections-diseases/rabies.html

  Rabies is a fatal, acute, progressive encephalomyelitis caused by neurotropic viruses in the family Rhabdoviridae, genus Lyssavirus. Numerous, diverse lyssaviruses are found in various mammalian species throughout the world, all of which can cause fatal human rabies. Rabies virus is by far the most common Lyssavirus infection in humans. Tens of millions of potential human exposures and tens of thousands of deaths from rabies occur each year. […] The normal and most successful mode of rabies virus transmission is via the bite of a rabid animal. Rabies virus is neurotropic; it gains access to the nervous system through exposed peripheral nerve synapses after inoculation, most often through bite wounds. The virus travels from its point of entry within peripheral nerves to the central nervous system (CNS), where viral replication increases exponentially. Rabies virus then migrates from the CNS back to the peripheral nervous system (PNS) into, among other innervated tissues, the salivary glands. Rabies virus secreted in saliva allows the transmission cycle to repeat.

• #2 Rabies Virus Hijacks and Accelerates the p75NTR Retrograde Axonal Transport Machinery | PLOS Pathogens

  https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1004348

  The strategy RABV uses to hijack the cellular transport machinery is unknown. […] Here we show that RABV binds to and is internalized together with p75NTR, forming endocytic compartments which undergo processive long distance transport. […] Our model suggests that RABV may enter the cell by receptor-mediated endocytosis following its binding to p75NTR, after which it enhances the efficiency of the retrograde co-transport of RABV p75NTR complexes. […] RABV is internalized at the axon tip, in part by exploiting the p75NTR pathway. […] RABV binding to p75NTR allows the virus to exploit a rapid transport mechanism to facilitate its trafficking to the cell body.

• #2 Rabies pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Rabies_pathophysiology

  The rabies virus is categorized as a Lyssavirus. The primary mechanism involved in the neuroinvasion of RV is trans-synaptic neuronal spread. RV infects neurons and leads to the degeneration of the neuronal processes by disrupting cytoskeletal integrity. […] The main mechanism involved in the neuroinvasion of RV is trans-synaptic neuronal spread. The following proteins lead to the spread of virus between the neurons, once the virus gains entry into the body: Rabies virus G protein (glycoprotein): RV to spread from the post-synaptic site to the pre-synaptic site. Rabies virus P protein (a cofactor for RNA polymerase): important determinant of retrograde transport of the virus within axons. […] Trans-synaptic neuronal spread leads to spread of infection to the CNS from the peripheral nerves. RV forms cytoplasmic inclusion bodies called Negri bodies in the neurons, which are composed of the viral N and P proteins (all viral RNAs genome, antigenome, and every mRNA have been known to be found inside the inclusion bodies- suggesting that they play a role in viral replication and life cycle). RV infects neurons and leads to degeneration of the neuronal processes by disrupting cytoskeletal integrity. The hypothalamus is understood to be affected most severely by RV infection.

• #2 Transmission and pathogenesis | Rabies – Bulletin – Europe

  https://www.who-rabies-bulletin.org/site-page/transmission-and-pathogenesis

  In most cases the disease is transmitted via the bite of rabid animals which shed infectious virus with their saliva. The virus enters the body through transdermal inoculation (i.e. wounds) or direct contact of infectious material (i.e. saliva, cerebrospinal liquid, nerve tissue) to mucous membranes or skin lesions. The virus can not penetrate intact skin. […] After entry the virus binds to cell receptors. Viruses may replicate within striated muscle cells ore directly infect nerve cells. […] The virus then travels via retrograde axoplasmatic transport mechanisms to the central nervous system. Both motor and sensory fibres may be involved depending on the animal infected. […] Once it has reached the CNS, rapid virus replication takes place, causing pathologic effects on nerve cell physiology. The virus then moves from the CNS via anterograde axoplasmic flow within peripheral nerves, leading to infection of some of the adjacent non-nervous tissues, for example, secretory tissues of salivary glands. The virus is widely disseminated throughout the body at the time of clinical onset. With shedding of infectious virus in saliva the infection cycle of rabies is completed.

• #2 Research may reveal how rabies induces frenzied behavior | UAF news and information

  https://news.uaf.edu/research-may-reveal-how-rabies-induces-specific-behavior/

  We knew that nicotinic acetylcholine receptors, which bind to the virus in muscles, are also found in the brain, and we presumed that virus could also bind to such receptors. […] Hueffer then teamed with another co-author, Michael Harris, to develop experiments to demonstrate whether the rabies virus glycoprotein alters behavior in animals. […] We thought that if viruses could bind to receptors in these spaces and change how brain cells normally communicate, the virus could change behavior of the infected animal. […] This change of behavior could work to the advantage of the virus, changing the behavior of infected animals to increase the chances that infection will spread to other animals. […] Hueffer said that this is the first experimental evidence showing a molecular mechanism inducing a specific behavioral change in a host that favors a diseases transmission.

• #2 What is the mechanism of Rabies Vaccine Adsorbed?

  https://synapse.patsnap.com/article/what-is-the-mechanism-of-rabies-vaccine-adsorbed

  4. Formation of Memory Cells: Alongside the production of antibodies, some of the activated B cells and T cells become memory cells. These cells persist in the body for a long time, often years or even a lifetime. Memory cells provide long-term immunity by enabling a faster and stronger immune response if the individual is exposed to the rabies virus in the future. […] 5. Adjuvant Role: The adjuvants used in the Rabies Vaccine Adsorbed play a crucial role by enhancing the overall immune response. They work by creating a depot effect, whereby the antigens are released slowly over time, providing prolonged exposure and stimulation to the immune system. Additionally, adjuvants can stimulate the recruitment and activation of more immune cells at the site of injection, further boosting the efficacy of the vaccine.

• #2 Rabies Virus Genome: Pathogenesis, Evolutionary Origins, and Immunological Perspectives – CD Genomics

  https://www.cd-genomics.com/resource-rabies-virus-genome-pathogenesis-evolutionary.html

  Rabies is a highly fatal neurological disease caused by rabies virus infection. […] We will introduce the structure of the virus, its transmission pathways, key pathogenic factors, and how it evades the host immune system. […] The successful implementation of the RABV life cycle depends on the preservation of the neuronal network. […] Rabies virus usually invades the human body through damaged skin or mucous membrane. […] The virus spreads centripetal towards the central nerve along the axon of the nerve at a fast speed, and thrives in large numbers to the dorsal root ganglia of the spinal cord. […] When the virus damages the vagus, glossopharyngeal and sublingual brain nerve nuclei, it will cause spasm of the swallowing muscles and respiratory muscles, causing patients to experience symptoms such as water phobia, swallowing and difficulty breathing.

Zobacz więcej