The emergence of the novel ß-coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a global pandemic of coronavirus disease 2019 (COVID-19). Clinical studies have documented that potentially severe neurological symptoms are associated with SARS-CoV-2 infection, thereby suggesting direct CNS penetration by the virus. Prior studies have demonstrated that the destructive neurological effects of rabies virus (RABV) infections are mediated by CNS transport of the virus tightly bound to the nicotinic acetylcholine receptor (nAChR). By comparison, it has been hypothesized that a similar mechanism exists to explain the multiple neurological effects of SARS-CoV-2 via binding to peripheral nAChRs followed by orthograde or retrograde transport into the CNS. Genetic engineering of the RABV has been employed to generate novel vaccines consisting of non-replicating RABV particles expressing chimeric capsid proteins containing human immunodeficiency virus 1 (HIV-1), Middle East respiratory syndrome (MERS-CoV), Ebolavirus, and hepatitis C virus (HCV) sequences. Accordingly, we present a critical discussion that integrates lessons learned from prior RABV research and vaccine development into a working model of a SARS-CoV-2 vaccine that selectively targets and neutralizes CNS penetration of a tightly bound viral nAChR complex.

• MeSH
• Betacoronavirus chemie   imunologie   MeSH
• glykoprotein S, koronavirus chemie   genetika   imunologie   MeSH
• koronavirové infekce imunologie   metabolismus   prevence a kontrola   virologie   MeSH
• lidé MeSH
• nikotinové receptory metabolismus   MeSH
• pandemie MeSH
• proteinové domény MeSH
• replikace viru * MeSH
• virová pneumonie imunologie   virologie   MeSH
• virové vakcíny chemie   imunologie   metabolismus   MeSH
• virus vztekliny genetika   fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Rabies is a deadly viral disease with an extremely high fatality rate in humans. Previously, it was suggested that an enhancement of the blood-brain barrier (BBB) permeability, which allows immune cells and/or antibodies to enter the central nervous system (CNS) tissue, is critical to clear the infection. In this study, we utilised mannitol to increase BBB permeability in mice infected with highly pathogenic silver-haired bat rabies virus (SHBRV). We found that intraperitoneal injection of mannitol causes a slight, transient increase of BBB permeability in the treated mice. SHBRV-infected mice were treated with intraperitoneally administered mannitol daily from day 3 or day 4 post-infection, but no effect of this treatment on the time of disease onset, clinical signs or survival was observed. This data indicates that the increase of BBB permeability by mannitol is not efficient in promoting CNS virus clearance in SHBRV-infected mice.

• MeSH
• antigeny virové metabolismus   MeSH
• centrální nervový systém účinky léků   metabolismus   MeSH
• hematoencefalická bariéra účinky léků   metabolismus   MeSH
• mannitol terapeutické užití   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• protilátky virové metabolismus   MeSH
• virus vztekliny účinky léků   patogenita   MeSH
• vzteklina farmakoterapie   virologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Recent studies demonstrated that inhibitors of pro-inflammatory molecular cascades triggered by rabies infection in the central nervous system (CNS) can enhance survival in mouse model and that certain antiviral compounds interfere with rabies virus replication in vitro. In this study different combinations of therapeutics were tested to evaluate their effect on survival in rabies-infected mice, as well as on viral load in the CNS. C57Bl/6 mice were infected with Silver-haired bat rabies virus (SHBRV)-18 at virus dose approaching LD50 and LD100. In one experimental group daily treatments were initiated 4 h before-, in other groups 48 or 96 h after challenge. In the first experiment therapeutic combination contained inhibitors of tumour necrosis factor-α (infliximab), caspase-1 (Ac-YVAD-cmk), and a multikinase inhibitor (sorafenib). In the treated groups there was a notable but not significant increase of survival compared to the virus infected, non-treated mice. The addition of human rabies immunoglobulins (HRIG) to the combination in the second experiment almost completely prevented mortality in the pre-exposure treatment group along with a significant reduction of viral titres in the CNS. Post-exposure treatments also greatly improved survival rates. As part of the combination with immunomodulatory compounds, HRIG had a higher impact on survival than alone. In the third experiment the combination was further supplemented with type-I interferons, ribavirin and favipiravir (T-705). As a blood-brain barrier opener, mannitol was also administered. This treatment was unable to prevent lethal consequences of SHBRV-18 infection; furthermore, it caused toxicity in treated mice, presumably due to interaction among the components. In all experiments, viral loads in the CNS were similar in mice that succumbed to rabies regardless of treatment. According to the findings, inhibitors of detrimental host response to rabies combined with antibodies can be considered among the possible therapeutic and post-exposure options in human rabies cases.

• MeSH
• antivirové látky terapeutické užití   MeSH
• imunoglobuliny terapeutické užití   MeSH
• imunohistochemie MeSH
• Kaplanův-Meierův odhad MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• protilátky virové imunologie   MeSH
• replikace viru účinky léků   MeSH
• tělesná hmotnost účinky léků   MeSH
• virus vztekliny účinky léků   imunologie   patogenita   MeSH
• vzteklina farmakoterapie   imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• epidemiologie MeSH
• očkovací programy MeSH
• vakcína proti vzteklině MeSH
• virus vztekliny MeSH
• vzteklina prevence a kontrola   MeSH
• Publikační typ
• směrnice MeSH

• Konspekt
• Veřejné zdraví a hygiena
• NLK Obory
• epidemiologie
• infekční lékařství
• NLK Publikační typ
• publikace WHO

Anticipating how epidemics will spread across landscapes requires understanding host dispersal events that are notoriously difficult to measure. Here, we contrast host and virus genetic signatures to resolve the spatiotemporal dynamics underlying geographic expansions of vampire bat rabies virus (VBRV) in Peru. Phylogenetic analysis revealed recent viral spread between populations that, according to extreme geographic structure in maternally inherited host mitochondrial DNA, appeared completely isolated. In contrast, greater population connectivity in biparentally inherited nuclear microsatellites explained the historical limits of invasions, suggesting that dispersing male bats spread VBRV between genetically isolated female populations. Host nuclear DNA further indicated unanticipated gene flow through the Andes mountains connecting the VBRV-free Pacific coast to the VBRV-endemic Amazon rainforest. By combining Bayesian phylogeography with landscape resistance models, we projected invasion routes through northern Peru that were validated by real-time livestock rabies mortality data. The first outbreaks of VBRV on the Pacific coast of South America could occur by June 2020, which would have serious implications for agriculture, wildlife conservation, and human health. Our results show that combining host and pathogen genetic data can identify sex biases in pathogen spatial spread, which may be a widespread but underappreciated phenomenon, and demonstrate that genetic forecasting can aid preparedness for impending viral invasions.

• MeSH
• Bayesova věta MeSH
• biologická evoluce * MeSH
• Chiroptera virologie   MeSH
• genom virový MeSH
• interakce hostitele a patogenu * MeSH
• mikrosatelitní repetice genetika   MeSH
• roční období MeSH
• typy dědičnosti genetika   MeSH
• virus vztekliny genetika   MeSH
• vzteklina epidemiologie   MeSH
• zeměpis MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Geografické názvy
• Peru epidemiologie   MeSH

• MeSH
• Chiroptera MeSH
• Lyssavirus izolace a purifikace   klasifikace   MeSH
• virus vztekliny izolace a purifikace   klasifikace   MeSH
• vzteklina dějiny   diagnóza   etiologie   prevence a kontrola   přenos   veterinární   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

Nervová sústava je najkomplikovanejšou sústavou nášho organizmu a každé jej poškodenie zanecháva celoživotné následky. Rovnako ako je v neustálom vývoji veda a výskum, vyvíjajú sa aj vírusy. Ich vlastnosti a mechanizmy sa menia a prispôsobujú prostrediu, v ktorom sa nachádzajú. Z toho dôvodu je nevyhnutné študovať molekulárne vlastnosti vírusov, spôsoby, akými sa vyhýbajú imunitnej odpovedi a možnosti terapie a profylaxie. Cieľom nášho článku je podať komplexný prehľad o dvoch neuropatogénnych vírusoch rozšírených takmer po celom svete, víruse besnoty a víruse lymfocytovej choriomeningitídy a ich patogenéze, liečbe a profylaxii.

The nervous system is the most complicated system of our body and any damage leads to lifelong consequences. As well as the tireless development of science and research, evolve viruses too. Their properties and mechanisms of change adapt to the environment, in which they are located. Therefore, it is necessary to study the molecular properties of the viruses, the way they avoid the immune response, and the therapy and prophylaxis. The aim of this work is to give a comprehensive picture of two neuropathogenic viruses extended almost all over the world, rabies virus and lymphocytic choriomeningitis virus, including their pathogenesis, treatment and prophylaxis.

• MeSH
• lidé MeSH
• lymfocytární choriomeningitida * diagnóza   etiologie   prevence a kontrola   terapie   MeSH
• vakcína proti vzteklině dějiny   farmakologie   imunologie   terapeutické užití   MeSH
• virus lymfocytární choriomeningitidy klasifikace   patogenita   růst a vývoj   MeSH
• virus vztekliny patogenita   růst a vývoj   MeSH
• vzteklina * diagnóza   etiologie   prevence a kontrola   terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Although rabies incidence has fallen sharply over the past decades in Europe, the disease is still present in Eastern Europe. Oral rabies immunization of wild animal rabies has been shown to be the most effective method for the control and elimination of rabies. All rabies vaccines used in Europe are modified live virus vaccines based on the Street Alabama Dufferin (SAD) strain isolated from a naturally-infected dog in 1935. Because of the potential safety risk of a live virus which could revert to virulence, the genetic composition of three commercial attenuated live rabies vaccines was investigated in two independent laboratories using next genome sequencing. This study is the first one reporting on the diversity of variants in oral rabies vaccines as well as the presence of a mix of at least two different variants in all tested batches. The results demonstrate the need for vaccine producers to use new robust methodologies in the context of their routine vaccine quality controls prior to market release.

• MeSH
• atenuované vakcíny * MeSH
• divoká zvířata * MeSH
• genetická variace MeSH
• genom virový MeSH
• nemoci zvířat prevence a kontrola   MeSH
• RNA virová MeSH
• vakcína proti vzteklině genetika   imunologie   MeSH
• vakcinace veterinární   MeSH
• virus vztekliny genetika   imunologie   MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• vzteklina veterinární   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

• Klíčová slova
• virus MERS-CoV,
• MeSH
• Chiroptera * virologie   MeSH
• lidé MeSH
• virus Ebola MeSH
• virus Hendra MeSH
• virus Nipah MeSH
• virus SARS patogenita   MeSH
• virus vztekliny MeSH
• zdroje nemoci * virologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH

• MeSH
• atenuované vakcíny terapeutické užití   MeSH
• biomedicínský výzkum MeSH
• chřipka lidská epidemiologie   prevence a kontrola   virologie   MeSH
• hemoragická horečka Ebola prevence a kontrola   MeSH
• inaktivované vakcíny terapeutické užití   MeSH
• lidé MeSH
• objevování léků MeSH
• očkovací programy MeSH
• příušnice prevence a kontrola   MeSH
• rotavirové infekce prevence a kontrola   MeSH
• rozvojové země MeSH
• sekundární imunizace MeSH
• vakcína proti příušnicím terapeutické užití   MeSH
• vakcína proti rotavirům zásobování a distribuce   MeSH
• vakcína proti vzteklině terapeutické užití   MeSH
• vakcíny proti chřipce imunologie   MeSH
• vakcíny proti ebole MeSH
• virus Ebola imunologie   MeSH
• virus vztekliny imunologie   MeSH
• Check Tag
• lidé MeSH
• Geografické názvy
• Afrika MeSH
• Česká republika MeSH
• Súdán MeSH