scholarly journals Astrocytes in Flavivirus Infections

2019 ◽  
Vol 20 (3) ◽  
pp. 691 ◽  
Author(s):  
Maja Potokar ◽  
Jernej Jorgačevski ◽  
Robert Zorec
Keyword(s):  
Cell Types ◽  
Encephalitis Virus ◽  
Neural Cells ◽  
Virus Infections ◽  
Neurotropic Viruses ◽  
Neuronal Synapses ◽  
Tick Borne Encephalitis ◽  
The Central Nervous System ◽  
Tick Borne Encephalitis Virus ◽  
New Strategies

Virus infections of the central nervous system (CNS) can manifest in various forms of inflammation, including that of the brain (encephalitis) and spinal cord (myelitis), all of which may have long-lasting deleterious consequences. Although the knowledge of how different viruses affect neural cells is increasing, understanding of the mechanisms by which cells respond to neurotropic viruses remains fragmented. Several virus types have the ability to infect neural tissue, and astrocytes, an abundant and heterogeneous neuroglial cell type and a key element providing CNS homeostasis, are one of the first CNS cell types to get infected. Astrocytes are morphologically closely aligned with neuronal synapses, blood vessels, and ventricle cavities, and thereby have the capacity to functionally interact with neurons and endothelial cells. In this review, we focus on the responses of astrocytes to infection by neurotropic flaviviruses, including tick-borne encephalitis virus (TBEV), Zika virus (ZIKV), West Nile virus (WNV), and Japanese encephalitis virus (JEV), which have all been confirmed to infect astrocytes and cause multiple CNS defects. Understanding these mechanisms may help design new strategies to better contain and mitigate virus- and astrocyte-dependent neuroinflammation.

scholarly journals Methods for evaluating changes in permeability of the blood-brain barrier and liquor-blood barrier in experimental tick-borne encephalitis

2018 ◽  
pp. 30-36
Author(s):  
В.М. Курагина ◽  
О.В. Мотузова ◽  
Н.Н. Золотов ◽  
Г. Г. Карганова
Keyword(s):  
Viral Infection ◽  
Sodium Fluorescein ◽  
Circulatory Collapse ◽  
Dye Penetration ◽  
Neurotropic Viruses ◽  
Tick Borne Encephalitis ◽  
The Central Nervous System ◽  
Circulatory Disorders ◽  
Tick Borne Encephalitis Virus

Изучение взаимодействия нейротропных вирусов со структурами гематоэнцефалического барьера (ГЭБ) является наиболее интересной и малоизученной темой. Показано, что вирусы значительно различаются по характеру этого взаимодействия и используют различные механизмы для преодоления ГЭБ на пути в центральную нервную систему (ЦНС). Вирусы напрямую или опосредованно оказывают влияние на проницаемость ГЭБ. Изменение проницаемости гематоликворного барьера (ГЛБ) при вирусной инфекции не изучалось. Целью данной работы было определить информативность методов оценки изменения проницаемости ГЭБ и ГЛБ. Методы. Используя интраперитонеальное (и/п) и интраспинальное (и/с) введение флуоресцеина натрия животным, зараженным двумя штаммами вируса клещевого энцефалита, оценивали изменение проницаемости ГЭБ и ГЛБ по соотношению флуоресценции гомогената головного или спинного мозга и флуоресценции сыворотки крови. Результаты. В данной работе при вирусной инфекции было выявлено как увеличение проницаемости ГЭБ, так и снижение проникновения краски в ЦНС из крови при и/п введении красителя и в кровь при его и/с введении, что объясняется характерным для клещевого энцефалита нарушением гемодинамики и тяжелыми поражениями ЦНС. Вывод. Использование красителей при сочетании различных способов введения, помимо информации об изменении проницаемости ГЭБ и ГЛБ, дает комплексную оценку нарушения мозгового кровообращения при вирусной инфекции. Studying the interaction of neurotropic viruses with BBB structures is the most interesting and understudied subject. Viruses greatly differ in the nature of this interaction and use various mechanisms to overcome the BBB on the path to the central nervous system (CNS). Viruses affect permeability of the BBB directly or indirectly. Changes in permeability of the blood-cerebrospinal fluid barrier (BCB) have not been studied in viral infection. The aim of this study was to assess the informative value of methods for determination of changes in BBB and BCB permeability. Methods. Using intraperitoneal (i/p) and intraspinal (i/sp) sodium fluorescein injections changes in BBB and BCB permeability were measured by the ratio of cerebral or spinal cord homogenate fluorescence to serum fluorescence in mice infected with two strains of tick-borne encephalitis virus. Results. This study found both increased BBB permeability and decreased dye penetration from blood into the CNS following the i/p dye injection and into the blood following the i/sp dye injection in viral infection. This can be explained by the circulatory collapse and fatal injuries of the CNS typical for tick-borne encephalitis. Conclusion. Using different methods of dye injection provides a comprehensive assessment of cerebral circulatory disorders in viral infection in addition to information about changes in BBB and BCB permeability.

scholarly journals Tick-Borne Encephalitis Virus: A Quest for Better Vaccines against a Virus on the Rise

Vaccines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 451 ◽  
Author(s):  
Mareike Kubinski ◽  
Jana Beicht ◽  
Thomas Gerlach ◽  
Asisa Volz ◽  
Gerd Sutter ◽  
...  
Keyword(s):  
Antiviral Treatment ◽  
Encephalitis Virus ◽  
Protective Measure ◽  
Humoral And Cellular Immunity ◽  
Tick Borne Encephalitis ◽  
The Family ◽  
The Central Nervous System ◽  
Tick Borne Encephalitis Virus ◽  
Protection Against Infection ◽  
Vaccine Failures

Tick-borne encephalitis virus (TBEV), a member of the family Flaviviridae, is one of the most important tick-transmitted viruses in Europe and Asia. Being a neurotropic virus, TBEV causes infection of the central nervous system, leading to various (permanent) neurological disorders summarized as tick-borne encephalitis (TBE). The incidence of TBE cases has increased due to the expansion of TBEV and its vectors. Since antiviral treatment is lacking, vaccination against TBEV is the most important protective measure. However, vaccination coverage is relatively low and immunogenicity of the currently available vaccines is limited, which may account for the vaccine failures that are observed. Understanding the TBEV-specific correlates of protection is of pivotal importance for developing novel and improved TBEV vaccines. For affording robust protection against infection and development of TBE, vaccines should induce both humoral and cellular immunity. In this review, the adaptive immunity induced upon TBEV infection and vaccination as well as novel approaches to produce improved TBEV vaccines are discussed.

scholarly journals Tick-borne encephalitis virus infections in Germany. Seasonality and in-year patterns. A retrospective analysis from 2001-2018

PLoS ONE ◽  
2019 ◽  
Vol 14 (10) ◽  
pp. e0224044
Author(s):  
Johannes P. Borde ◽  
Klaus Kaier ◽  
Philip Hehn ◽  
Merle M. Böhmer ◽  
Teresa M. Kreusch ◽  
...  
Keyword(s):  
Retrospective Analysis ◽  
Encephalitis Virus ◽  
Virus Infections ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

scholarly journals Relation of genetic phylogeny and geographical distance of tick-borne encephalitis virus in central Europe

2011 ◽  
Vol 92 (8) ◽  
pp. 1906-1916 ◽  
Author(s):  
M. Weidmann ◽  
D. Růžek ◽  
K. Křivanec ◽  
G. Zöller ◽  
S. Essbauer ◽  
...  
Keyword(s):  
Czech Republic ◽  
Central Europe ◽  
Encephalitis Virus ◽  
Natural Focus ◽  
The Czech Republic ◽  
Tick Borne Encephalitis ◽  
Disease Pattern ◽  
The Central Nervous System ◽  
Tick Borne Encephalitis Virus ◽  
First Time

Tick-borne encephalitis virus (TBEV) is the most important arboviral agent causing disease of the central nervous system in central Europe. In this study, 61 TBEV E gene sequences derived from 48 isolates from the Czech Republic, and four isolates and nine TBEV strains detected in ticks from Germany, covering more than half a century from 1954 to 2009, were sequenced and subjected to phylogenetic and Bayesian phylodynamic analysis to determine the phylogeography of TBEV in central Europe. The general Eurasian continental east-to-west pattern of the spread of TBEV was confirmed at the regional level but is interlaced with spreading that arises because of local geography and anthropogenic influence. This spread is reflected by the disease pattern in the Czech Republic that has been observed since 1991. The overall evolutionary rate was estimated to be approximately 8×10−4 substitutions per nucleotide per year. The analysis of the TBEV E genes of 11 strains isolated at one natural focus in Žďár Kaplice proved for the first time that TBEV is indeed subject to local evolution.

Tick-borne encephalitis virus infections in Lithuanian domestic animals and ticks

2005 ◽  
Vol 37 (10) ◽  
pp. 742-746 ◽  
Author(s):  
Aurita Juceviciene ◽  
Milda Zygutiene ◽  
Pauli Leinikki ◽  
Henrikki Brummer-Korvenkontio ◽  
Mika Salminen ◽  
...  
Keyword(s):  
Domestic Animals ◽  
Encephalitis Virus ◽  
Virus Infections ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

Quality control assessment for the PCR diagnosis of tick-borne encephalitis virus infections

2007 ◽  
Vol 38 (1) ◽  
pp. 73-77 ◽  
Author(s):  
Oliver Donoso Mantke ◽  
Stephan W. Aberle ◽  
Tatjana Avšič-Županc ◽  
Milan Labuda ◽  
Matthias Niedrig
Keyword(s):  
Quality Control ◽  
Encephalitis Virus ◽  
Virus Infections ◽  
Tick Borne Encephalitis ◽  
Pcr Diagnosis ◽  
Tick Borne Encephalitis Virus

scholarly journals An E460D Substitution in the NS5 Protein of Tick-Borne Encephalitis Virus Confers Resistance to the Inhibitor Galidesivir (BCX4430) and Also Attenuates the Virus for Mice

2019 ◽  
Vol 93 (16) ◽  
Author(s):  
Ludek Eyer ◽  
Antoine Nougairède ◽  
Marie Uhlířová ◽  
Jean-Sélim Driouich ◽  
Darina Zouharová ◽  
...  
Keyword(s):  
Cell Culture ◽  
Yellow Fever Virus ◽  
Rna Virus ◽  
Encephalitis Virus ◽  
Viral Fitness ◽  
Virus Infections ◽  
Rna Dependent Rna Polymerase ◽  
Virus Inhibitor ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

ABSTRACT The adenosine analogue galidesivir (BCX4430), a broad-spectrum RNA virus inhibitor, has entered a phase 1 clinical safety and pharmacokinetics study in healthy subjects and is under clinical development for treatment of Ebola and yellow fever virus infections. Moreover, galidesivir also inhibits the reproduction of tick-borne encephalitis virus (TBEV) and numerous other medically important flaviviruses. Until now, studies of this antiviral agent have not yielded resistant viruses. Here, we demonstrate that an E460D substitution in the active site of TBEV RNA-dependent RNA polymerase (RdRp) confers resistance to galidesivir in cell culture. Galidesivir-resistant TBEV exhibited no cross-resistance to structurally different antiviral nucleoside analogues, such as 7-deaza-2′-C-methyladenosine, 2′-C-methyladenosine, and 4′-azido-aracytidine. Although the E460D substitution led to only a subtle decrease in viral fitness in cell culture, galidesivir-resistant TBEV was highly attenuated in vivo, with a 100% survival rate and no clinical signs observed in infected mice. Furthermore, no virus was detected in the sera, spleen, or brain of mice inoculated with the galidesivir-resistant TBEV. Our results contribute to understanding the molecular basis of galidesivir antiviral activity, flavivirus resistance to nucleoside inhibitors, and the potential contribution of viral RdRp to flavivirus neurovirulence. IMPORTANCE Tick-borne encephalitis virus (TBEV) is a pathogen that causes severe human neuroinfections in Europe and Asia and for which there is currently no specific therapy. We have previously found that galidesivir (BCX4430), a broad-spectrum RNA virus inhibitor, which is under clinical development for treatment of Ebola and yellow fever virus infections, has a strong antiviral effect against TBEV. For any antiviral drug, it is important to generate drug-resistant mutants to understand how the drug works. Here, we produced TBEV mutants resistant to galidesivir and found that the resistance is caused by a single amino acid substitution in an active site of the viral RNA-dependent RNA polymerase, an enzyme which is crucial for replication of the viral RNA genome. Although this substitution led only to a subtle decrease in viral fitness in cell culture, galidesivir-resistant TBEV was highly attenuated in a mouse model. Our results contribute to understanding the molecular basis of galidesivir antiviral activity.

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