A cluster of two human cases of tick-borne encephalitis (TBE) transmitted by unpasteurised goat milk and cheese in Germany, May 2016

So, Brockmann; Oehme, Rainer; Buckenmaier, T; Beer, Martin; Jeffery-Smith, Anna; Spannenkrebs, M; Haag-Milz, S; Wagner-Wiening, Christiane; Schlegel, C; Fritz, J; Zange, Sabine; Bestehorn, Malena; Lindau, Anne-Kathrin; Hoffmann, Donata; Tiberi, Simon; Mackenstedt, Ute; Dobler, Gerhard

doi:10.2807/1560-7917.es.2018.23.15.17-00336

Cited by 77 publications

(66 citation statements)

References 15 publications

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“…If such a model has existed for a long time, it should have resulted in a thoroughly intermixed Eurasian TBEV population, where identification of the types would not have been possible, but this is not the case. This observation is compatible with a recent diversification of TBEV in general and with the current rapid European TBEV expansion to novel areas and habitats [20,39,40,[62][63][64][65]. Predicted past population dynamics (Figure 9) is also in concordance with this data.…”

Section: Discussionsupporting

confidence: 85%

Tick-Borne Encephalitis Virus: An Emerging Ancient Zoonosis?

Deviatkin

Kholodilov

Vakulenko

et al. 2020

Viruses

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Tick-borne encephalitis (TBE) is one of the most important viral zoonosis transmitted by the bite of infected ticks. In this study, all tick-borne encephalitis virus (TBEV) E gene sequences available in GenBank as of June 2019 with known date of isolation (n = 551) were analyzed. Simulation studies showed that a sample bias could significantly affect earlier studies, because small TBEV datasets (n = 50) produced non-overlapping intervals for evolutionary rate estimates. An apparent lack of a temporal signal in TBEV, in general, was found, precluding molecular clock analysis of all TBEV subtypes in one dataset. Within all subtypes and most of the smaller groups in these subtypes, there was evidence of many medium- and long-distance virus transfers. These multiple random events may play a key role in the virus spreading. For some groups, virus diversity within one territory was similar to diversity over the whole geographic range. This is best exemplified by the virus diversity observed in Switzerland or Czech Republic. These two countries yielded most of the known European subtype Eu3 subgroup sequences, and the diversity of viruses found within each of these small countries is comparable to that of the whole Eu3 subgroup, which is prevalent all over Central and Eastern Europe. Most of the deep tree nodes within all three established TBEV subtypes dated less than 300 years back. This could be explained by the recent emergence of most of the known TBEV diversity. Results of bioinformatics analysis presented here, together with multiple field findings, suggest that TBEV may be regarded as an emerging disease.

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Section: Discussionsupporting

confidence: 85%

Tick-Borne Encephalitis Virus: An Emerging Ancient Zoonosis?

Deviatkin

Kholodilov

Vakulenko

et al. 2020

Viruses

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“…Astrocytes enter a reactive stage (6) and some of them die (7). Both neurons and astrocytes overexpressed a high level of chemokines involved in chemo-attraction of T cells in the brain parenchyma (8), although astrocytes are stronger producers. Figure was created using Servier Medical Art available on www.servier.com.…”

Section: Discussionmentioning

confidence: 99%

Pathological modeling of TBEV infection reveals differential innate immune responses in human neurons and astrocytes that correlate with their susceptibility to infection

Fares

Cochet-Bernoin

Gonzalez

et al. 2019

Preprint

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Tick-borne encephalitis virus (TBEV) is a member of the Flaviviridae family, Flavivirus genus, which includes several important human pathogens. It is responsible for neurological symptoms that may cause permanent disability or death, and, from a medical point of view, is the major arbovirus in Central/Northern Europe and North-eastern Asia. TBEV tropism is critical for neuropathogenesis, yet, little is known about the molecular mechanisms that govern the susceptibility of human brain cells to the virus. In this study, we sought to establish and characterize a new in vitro model of TBEV infection in the human brain and to decipher cell type-specific innate immunity and its relation to TBEV tropism and neuropathogenesis. We showed that infection of neuronal/glial cultures derived from human fetal neural progenitor cells (hNPCs) mimicked three major hallmarks of TBEV infection in the human brain, namely, preferential neuronal tropism, neuronal death and astrogliosis. We also showed that these cells had conserved their capacity to build an antiviral response against TBEV. TBEV-infected neuronal/glial cells, therefore, represented a highly relevant pathological model. By enriching the cultures in either human neurons or astrocytes, we further demonstrated qualitative and quantitative differential innate immune responses in the two cell types that correlated with their particular susceptibility to TBEV. Our results thus reveal that cell type-specific innate immunity is likely to contribute to shaping TBEV tropism for human brain cells. They offer a new in vitro model to further study TBEV-induced neuropathogenesis and improve our understanding of the mechanisms by which neurotropic viruses target and damage human brain cells.Author summaryTick-borne encephalitis virus (TBEV), a neurotropic Flavivirus that is responsible for encephalitis in humans, is of growing concern in Europe. Indeed, over the last two decades the number of reported cases has continuously increased and the virus has spread into new geographical areas. Whereas it is well established that neurons are the main target of TBEV in the human brain, the mechanisms that underlie this preferential tropism have not yet been elucidated. Here, we used neuronal/glial cells derived from human fetal neural progenitors to establish and characterize a new in vitro pathological model that mimics major hallmarks of TBEV infection in vivo; namely, neuronal tropism, neuronal death and astrogliosis. Using this highly relevant model, we showed that human neurons and astrocytes were both capable of developing an innate immune response against TBEV, but with dissimilar magnitudes that correlated with differential susceptibility to TBEV. Our results thus revealed that TBEV tropism for subsets of human brain cells is likely to depend on cell-type specific innate immunity. This improves our understanding of the mechanisms by which neurotropic viruses target and damage human brain cells and may help guide development of future therapies.

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“…TBEV is usually transmitted to humans from infected ticks, mainly of the Ixodes family, but may occasionally be acquired by consumption of unpasteurized dairy products from infected livestock [7][8][9]. Upon inoculation into the human skin, initial infection and replication occur in local dendritic cells (DCs).…”

Section: Introductionmentioning

confidence: 99%

Pathological modeling of TBEV infection reveals differential innate immune responses in human neurons and astrocytes that correlate with their susceptibility to infection

Fares

Cochet-Bernoin

Gonzalez

et al. 2020

J Neuroinflammation

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Background: Tick-borne encephalitis virus (TBEV) is a member of the Flaviviridae family, Flavivirus genus, which includes several important human pathogens. It is responsible for neurological symptoms that may cause permanent disability or death, and, from a medical point of view, is the major arbovirus in Central/Northern Europe and North-Eastern Asia. TBEV tropism is critical for neuropathogenesis, yet little is known about the molecular mechanisms that govern the susceptibility of human brain cells to the virus. In this study, we sought to establish and characterize a new in vitro model of TBEV infection in the human brain and to decipher cell type-specific innate immunity and its relation to TBEV tropism and neuropathogenesis.Method: Human neuronal/glial cells were differentiated from neural progenitor cells and infected with the TBEV-Hypr strain. Kinetics of infection, cellular tropism, and cellular responses, including innate immune responses, were characterized by measuring viral genome and viral titer, performing immunofluorescence, enumerating the different cellular types, and determining their rate of infection and by performing PCR array and qRT-PCR. The specific response of neurons and astrocytes was analyzed using the same approaches after enrichment of the neuronal/glial cultures for each cellular subtype. Results: We showed that infection of human neuronal/glial cells mimicked three major hallmarks of TBEV infection in the human brain, namely, preferential neuronal tropism, neuronal death, and astrogliosis. We further showed that these cells conserved their capacity to mount an antiviral response against TBEV. TBEV-infected neuronal/glial cells, therefore, represented a highly relevant pathological model. By enriching the cultures for either neurons or astrocytes, we further demonstrated qualitative and quantitative differential innate immune responses in the two cell types that correlated with their particular susceptibility to TBEV. Conclusion:Our results thus reveal that cell type-specific innate immunity is likely to contribute to shaping TBEV tropism for human brain cells. They describe a new in vitro model for in-depth study of TBEV-induced neuropathogenesis and improve our understanding of the mechanisms by which neurotropic viruses target and damage human brain cells.

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A cluster of two human cases of tick-borne encephalitis (TBE) transmitted by unpasteurised goat milk and cheese in Germany, May 2016

Cited by 77 publications

References 15 publications

Tick-Borne Encephalitis Virus: An Emerging Ancient Zoonosis?

Tick-Borne Encephalitis Virus: An Emerging Ancient Zoonosis?

Pathological modeling of TBEV infection reveals differential innate immune responses in human neurons and astrocytes that correlate with their susceptibility to infection

Pathological modeling of TBEV infection reveals differential innate immune responses in human neurons and astrocytes that correlate with their susceptibility to infection

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