scholarly journals ADAM15 participates in tick-borne encephalitis virus replication

2020 ◽  
Author(s):  
Qi Yang ◽  
Rongjuan Pei ◽  
Yun Wang ◽  
Yuan Zhou ◽  
Min Yang ◽  
...  
Keyword(s):  
Life Cycle ◽  
Cellular Localization ◽  
Encephalitis Virus ◽  
Host Factors ◽  
Host Protein ◽  
Sequencing Analysis ◽  
Viral Pathogen ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Tbev Infection

Tick-borne encephalitis virus (TBEV), a major tick-borne viral pathogen of humans, is known to cause neurological diseases such as meningitis, encephalitis and meningoencephalitis. However, the life cycle and pathogenesis of TBEV are not well understood. Here, we show that the knockdown or knockout of ADAM15 (a disintegrin and metalloproteinase 15), a host protein involved in neuroblastoma diseases, leads to TBEV replication and assembly defects. We characterized the disintegrin domain in ADAM15 and found that the ADAM15 subcellular localization was changed following TBEV infection. RNAi screen analysis confirmed the non-redundant ADAM’s functions and identified a specific role for ADAM15 in TBEV infection. An RNA-sequencing analysis was also conducted to understand the causal link between TBEV infection and the cellular endomembrane network, namely, the generation of replication organelles promoting viral genome replication and virus production. Our data demonstrated that TBEV infection changes ADAM15 cellular localization, which contributes to membrane reorganization and viral replication. Importance Tick populations are increasing and their geographic ranges are expanding. Increases in tick-borne disease prevalence and transmission are important public health issues. Tick-borne encephalitis virus (TBEV) often results in meningitis, encephalitis and meningoencephalitis. TBEV causes clinical disease in more than 10,000 to 20,000 humans in Europe and Asia per year. An increased incidence of TBE has been noted in Europe and Asia, as a consequence of climate and socioeconomic changes. The need to investigate the mechanism(s) of the interaction between the virus and the host factors is apparent, which helps to understand the roles of host factors related to the life cycle of TBEV. The significance of our research is in identifying the ADAM15 for TBEV replication, which will greatly enhance our understanding of TBEV life cycle and highlight a target for pharmaceutical consideration.

scholarly journals Infection and injury of human astrocytes by tick-borne encephalitis virus

2014 ◽  
Vol 95 (11) ◽  
pp. 2411-2426 ◽  
Author(s):  
Martin Palus ◽  
Tomáš Bílý ◽  
Jana Elsterová ◽  
Helena Langhansová ◽  
Jiří Salát ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Encephalitis Virus ◽  
Ultrastructural Changes ◽  
Interferon Α ◽  
Human Astrocytes ◽  
Tick Borne Encephalitis ◽  
Infected Cells ◽  
Tick Borne Encephalitis Virus ◽  
Tbev Infection ◽  
Pro Inflammatory Cytokines

Tick-borne encephalitis (TBE), a disease caused by tick-borne encephalitis virus (TBEV), represents the most important flaviviral neural infection in Europe and north-eastern Asia. In the central nervous system (CNS), neurons are the primary target for TBEV infection; however, infection of non-neuronal CNS cells, such as astrocytes, is not well understood. In this study, we investigated the interaction between TBEV and primary human astrocytes. We report for the first time, to the best of our knowledge, that primary human astrocytes are sensitive to TBEV infection, although the infection did not affect their viability. The infection induced a marked increase in the expression of glial fibrillary acidic protein, a marker of astrocyte activation. In addition, expression of matrix metalloproteinase 9 and several key pro-inflammatory cytokines/chemokines (e.g. tumour necrosis factor α, interferon α, interleukin (IL)-1β, IL-6, IL-8, interferon γ-induced protein 10, macrophage inflammatory protein, but not monocyte chemotactic protein 1) was upregulated. Moreover, we present a detailed description of morphological changes in TBEV-infected cells, as investigated using three-dimensional electron tomography. Several novel ultrastructural changes were observed, including the formation of unique tubule-like structures of 17.9 ±0.15 nm diameter with associated viral particles and/or virus-induced vesicles and located in the rough endoplasmic reticulum of the TBEV-infected cells. This is the first demonstration that TBEV infection activates primary human astrocytes. The infected astrocytes might be a potential source of pro-inflammatory cytokines in the TBEV-infected brain, and might contribute to the TBEV-induced neurotoxicity and blood–brain barrier breakdown that occurs during TBE. The neuropathological significance of our observations is also discussed.

scholarly journals A Functional Toll-Like Receptor 3 Gene (TLR3) May Be a Risk Factor for Tick-borne Encephalitis Virus (TBEV) Infection

2011 ◽  
Vol 203 (4) ◽  
pp. 523-528 ◽  
Author(s):  
Elin Kindberg ◽  
Sirkka Vene ◽  
Aukse Mickiene ◽  
Åke Lundkvist ◽  
Lars Lindquist ◽  
...  
Keyword(s):  
Risk Factor ◽  
Encephalitis Virus ◽  
Toll Like Receptor ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Tbev Infection

scholarly journals Nucleoside Inhibitors of Tick-Borne Encephalitis Virus

2015 ◽  
Vol 59 (9) ◽  
pp. 5483-5493 ◽  
Author(s):  
Luděk Eyer ◽  
James J. Valdés ◽  
Victor A. Gil ◽  
Radim Nencka ◽  
Hubert Hřebabecký ◽  
...  
Keyword(s):  
Neuroblastoma Cells ◽  
Antiviral Effect ◽  
Encephalitis Virus ◽  
Nucleoside Analogues ◽  
Kidney Cells ◽  
Porcine Kidney ◽  
Human Neuroblastoma ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Tbev Infection

ABSTRACTTick-borne encephalitis virus (TBEV) is a leading cause of human neuroinfections in Europe and Northeast Asia. There are no antiviral therapies for treating TBEV infection. A series of nucleoside analogues was tested for the ability to inhibit the replication of TBEV in porcine kidney cells and human neuroblastoma cells. The interactions of three nucleoside analogues with viral polymerase were simulated using advanced computational methods. The nucleoside analogues 7-deaza-2′-C-methyladenosine (7-deaza-2′-CMA), 2′-C-methyladenosine (2′-CMA), and 2′-C-methylcytidine (2′-CMC) inhibited TBEV replication. These compounds showed dose-dependent inhibition of TBEV-induced cytopathic effects, TBEV replication (50% effective concentrations [EC50]of 5.1 ± 0.4 μM for 7-deaza-2′-CMA, 7.1 ± 1.2 μM for 2′-CMA, and 14.2 ± 1.9 μM for 2′-CMC) and viral antigen production. Notably, 2′-CMC was relatively cytotoxic to porcine kidney cells (50% cytotoxic concentration [CC50] of ∼50 μM). The anti-TBEV effect of 2′-CMA in cell culture diminished gradually after day 3 posttreatment. 7-Deaza-2′-CMA showed no detectable cellular toxicity (CC50> 50 μM), and the antiviral effect in culture was stable for >6 days posttreatment. Computational molecular analyses revealed that compared to the other two compounds, 7-deaza-2′-CMA formed a large cluster near the active site of the TBEV polymerase. High antiviral activity and low cytotoxicity suggest that 7-deaza-2′-CMA is a promising candidate for further investigation as a potential therapeutic agent in treating TBEV infection.

TBE in France

2019 ◽  
Author(s):  
Yves Hansmann ◽  
Aurélie Velay
Keyword(s):  
Human Case ◽  
Encephalitis Virus ◽  
Eastern Region ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Tbev Infection

The first human case of tick-borne encephalitis virus (TBEV) infection in France was reported in 1968 in Alsace, an eastern region next to the German border: a gamekeeper working in a forest near Strasbourg.

scholarly journals Flaviviridae Viruses and Oxidative Stress: Implications for Viral Pathogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Zhenzhen Zhang ◽  
Liang Rong ◽  
Yi-Ping Li
Keyword(s):  
Oxidative Stress ◽  
Life Cycle ◽  
Viral Proteins ◽  
Viral Pathogenesis ◽  
Encephalitis Virus ◽  
Research Attention ◽  
Molecular Events ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
And Oxidative Stress

Oxidative stress is induced once the balance of generation and neutralization of reactive oxygen species (ROS) is broken in the cell, and it plays crucial roles in a variety of natural and diseased processes. Infections of Flaviviridae viruses trigger oxidative stress, which affects both the cellular metabolism and the life cycle of the viruses. Oxidative stress associated with specific viral proteins, experimental culture systems, and patient infections, as well as its correlations with the viral pathogenesis attracts much research attention. In this review, we primarily focus on hepatitis C virus (HCV), dengue virus (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), West Nile virus (WNV), and tick-borne encephalitis virus (TBEV) as representatives of Flaviviridae viruses and we summarize the mechanisms involved in the relevance of oxidative stress for virus-associated pathogenesis. We discuss the current understanding of the pathogenic mechanisms of oxidative stress induced by Flaviviridae viruses and highlight the relevance of autophagy and DNA damage in the life cycle of viruses. Understanding the crosstalk between viral infection and oxidative stress-induced molecular events may offer new avenues for antiviral therapeutics.

scholarly journals Proteome-wide cross-linking mass spectrometry to identify specific virus capsid-host interactions between tick-borne encephalitis virus and neuroblastoma cells

2021 ◽  
Author(s):  
Sarah V Barrass ◽  
Lauri I A Pulkkinen ◽  
Olli Vapalahti ◽  
Suvi Kuivanen ◽  
Maria Anastasina ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Protein Interactions ◽  
Neuroblastoma Cells ◽  
Encephalitis Virus ◽  
Host Protein ◽  
Cross Linking ◽  
Host Proteins ◽  
Host Interactions ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus

Virus-host protein-protein interactions are central to viral infection, but are challenging to identify and characterise, especially in complex systems involving intact viruses and cells. In this work, we demonstrate a proteome-wide approach to identify virus-host interactions using chemical cross-linking coupled with mass spectrometry. We adsorbed tick-borne encephalitis virus onto metabolically-stalled neuroblastoma cells, covalently cross-linked interacting virus-host proteins, and performed limited proteolysis to release primarily the surface-exposed proteins for identification by mass spectrometry. Using the intraviral protein cross-links as an internal control to assess cross-link confidence levels, we identified 22 high confidence unique intraviral cross-links and 59 high confidence unique virus-host protein-protein interactions. The identified host proteins were shown to interact with eight distinct sites on the outer surface of the virus. Notably, we identified an interaction between the substrate-binding domain of heat shock protein family A member 5, an entry receptor for four related flaviviruses, and the hinge region of the viral envelope protein. We also identified host proteins involved in endocytosis, cytoskeletal rearrangement, or located in the cytoskeleton, suggesting that entry mechanisms for tick-borne encephalitis virus could include both clathrin-mediated endocytosis and macropinocytosis. Additionally, cross-linking of the viral proteins showed that the capsid protein forms dimers within tick-borne encephalitis virus, as previously observed with purified C proteins for other flaviviruses. This method enables the identification and mapping of transient virus-host interactions, under near-physiological conditions, without the need for genetic manipulation.

scholarly journals First human case of tick-borne encephalitis virus infection acquired in the Netherlands, July 2016

2016 ◽  
Vol 21 (33) ◽  
Author(s):  
Joris A de Graaf ◽  
Johan H J Reimerink ◽  
G Paul Voorn ◽  
Elisabeth A bij de Vaate ◽  
Ankje de Vries ◽  
...  
Keyword(s):  
Virus Infection ◽  
The Netherlands ◽  
Human Case ◽  
Encephalitis Virus ◽  
Tick Bite ◽  
Travel History ◽  
Qrt Pcr ◽  
Tick Borne Encephalitis ◽  
Tick Borne Encephalitis Virus ◽  
Tbev Infection

In July 2016, the first autochthonous case of tick-borne encephalitis was diagnosed in the Netherlands, five days after a report that tick-borne encephalitis virus (TBEV) had been found in Dutch ticks. A person in their 60s without recent travel history suffered from neurological symptoms after a tick bite. TBEV serology was positive and the tick was positive in TBEV qRT-PCR. TBEV infection should be considered in patients with compatible symptoms in the Netherlands.

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