Signaling events evoked by domain III of envelop glycoprotein of tick-borne encephalitis virus and West Nile virus in human brain microvascular endothelial cells

Bhide, Katarína; Mochnáčová, Evelína; Tkáčová, Zuzana; Petroušková, Patrícia; Kulkarni, Amod; Bhide, Mangesh

doi:10.1038/s41598-022-13043-1

Cited by 3 publications

(3 citation statements)

References 110 publications

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“…Reverse transcription of RNA (1 µg) into cDNA was performed using random hexamer primers as described previously ( Bhide et al., 2022 ). mRNA levels of DEGs were corroborated with qPCR using 6 ng of cDNA, 10 pmol of gene specific primers ( Supplementary Table 2 , primers designed with Geneious Pro software) and Sybr green chemistry on StepOnePlus Real-Time PCR System ( Bhide et al., 2022 ). The average of threshold cycle (Ct) values of two reference genes - β2-microtubulin and glyceraldehyde 3-phosphate dehydrogenase was used for normalization.…”

Section: Methodsmentioning

confidence: 99%

“…The average of threshold cycle (Ct) values of two reference genes - β2-microtubulin and glyceraldehyde 3-phosphate dehydrogenase was used for normalization. The relative gene expression (2 -ΔΔCt ) and log 2 fold change (Log 2 FC) was determined as described before ( Bhide et al., 2022 ). Pearson correlation coefficient (r) was calculated between the Log 2 FC values of RNA-seq and qRT-PCR using Graphpad.…”

Section: Methodsmentioning

confidence: 99%

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Differential transcriptome response of blood brain barrier spheroids to neuroinvasive Neisseria and Borrelia

Kulkarni,

Jozefiaková,

Bhide

et al. 2023

Front. Cell. Infect. Microbiol.

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BackgroundThe blood-brain barrier (BBB), a highly regulated interface between the blood and the brain, prevents blood-borne substances and pathogens from entering the CNS. Nevertheless, pathogens like Neisseria meningitidis and Borrelia bavariensis can breach the BBB and infect the brain parenchyma. The self-assembling BBB-spheroids can simulate the cross talk occurring between the cells of the barrier and neuroinvasive pathogens.MethodsBBB spheroids were generated by co-culturing human brain microvascular endothelial cells (hBMECs), pericytes and astrocytes. The BBB attributes of spheroids were confirmed by mapping the localization of cells, observing permeability of angiopep2 and non-permeability of dextran. Fluorescent Neisseria, Borrelia or E. coli (non-neuroinvasive) were incubated with spheroids to observe the adherence, invasion and spheroid integrity. Transcriptome analysis with NGS was employed to investigate the response of BBB cells to infections.ResultshBMECs were localized throughout the spheroids, whereas pericytes and astrocytes were concentrated around the core. Within 1 hr of exposure, Neisseria and Borrelia adhered to spheroids, and their microcolonization increased from 5 to 24 hrs. Integrity of spheroids was compromised by both Neisseria and Borrelia, but not by E. coli infection. Transcriptome analysis revealed a significant change in the expression of 781 genes (467 up and 314 down regulated) in spheroids infected with Neisseria, while Borrelia altered the expression of 621 genes (225 up and 396 down regulated). The differentially expressed genes could be clustered into various biological pathways like cell adhesion, extracellular matrix related, metallothionines, members of TGF beta, WNT signaling, and immune response. Among the differentially expressed genes, 455 (48%) genes were inversely expressed during Neisseria and Borrelia infection.ConclusionThe self-assembling spheroids were used to perceive the BBB response to neuroinvasive pathogens - Neisseria and Borrelia. Compromised integrity of spheroids during Neisseria and Borrelia infection as opposed to its intactness and non-adherence of E. coli (non-neuroinvasive) denotes the pathogen dependent fate of BBB. Genes categorized into various biological functions indicated weakened barrier properties of BBB and heightened innate immune response. Inverse expression of 48% genes commonly identified during Neisseria and Borrelia infection exemplifies unique response of BBB to varying neuropathogens.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Differential transcriptome response of blood brain barrier spheroids to neuroinvasive Neisseria and Borrelia

Kulkarni,

Jozefiaková,

Bhide

et al. 2023

Front. Cell. Infect. Microbiol.

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“…TBEV has been shown to establish a productive infection of cells comprising the BBB, including the human brain microvascular endothelial cells (hBMECs) [97], pericytes [98], and astrocytes [49,98,99]. Studies of gene expression in hBMECs treated with recombinant envelope protein (domain III, rDIII) from TBEV have revealed an upregulation of genes associated with virus uptake, tight junction disruption, extracellular matrix reorganization, and the activation of innate immunity [100].…”

Section: Tbevmentioning

confidence: 99%

T Cells in Tick-Borne Flavivirus Encephalitis: A Review of Current Paradigms in Protection and Disease Pathology

Stone

Pinto

2023

Viruses

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The family Flaviviridae is comprised of a diverse group of arthropod-borne viruses that are the etiological agents of globally relevant diseases in humans. Among these, infection with several of these flaviviruses—including West Nile virus (WNV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), tick-borne encephalitis virus (TBEV), and Powassan virus (POWV)—can result in neuroinvasive disease presenting as meningitis or encephalitis. Factors contributing to the development and resolution of tick-borne flavivirus (TBEV, POWV) infection and neuropathology remain unclear, though many recently undertaken studies have described the virus–host interactions underlying encephalitic disease. With access to neural tissues despite the selectively permeable blood–brain barrier, T cells have emerged as one notable contributor to neuroinflammation. The goal of this review is to summarize the recent advances in tick-borne flavivirus immunology—particularly with respect to T cells—as it pertains to the development of encephalitis. We found that although T cell responses are rarely evaluated in a clinical setting, they are integral in conjunction with antibody responses to restricting the entry of TBFV into the CNS. The extent and means by which they can drive immune pathology, however, merits further study. Understanding the role of the T cell compartment in tick-borne flavivirus encephalitis is instrumental for improving vaccine safety and efficacy, and has implications for treatments and interventions for human disease.

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Inflammatory Response Associated with West Nile Neuroinvasive Disease: A Systematic Review

Pavesi,

Tiecco,

Rossi

et al. 2024

Viruses

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Background: West Nile virus (WNV) infection is a seasonal arbovirosis with the potential to cause severe neurological disease. Outcomes of the infection from WNV depend on viral factors (e.g., lineage) and host-intrinsic factors (e.g., age, sex, immunocompromising conditions). Immunity is essential to control the infection but may also prove detrimental to the host. Indeed, the persistence of high levels of pro-inflammatory cytokines and chemokines is associated with the development of blood–brain barrier (BBB) damage. Due to the importance of the inflammatory processes in the development of West Nile neuroinvasive disease (WNND), we reviewed the available literature on the subject. Methods: According to the 2020 updated PRISMA guidelines, all peer-reviewed articles regarding the inflammatory response associated with WNND were included. Results: One hundred and thirty-six articles were included in the data analysis and sorted into three groups (in vitro on-cell cultures, in vivo in animals, and in humans). The main cytokines found to be increased during WNND were IL-6 and TNF-α. We highlighted the generally small quantity and heterogeneity of information about the inflammatory patterns associated with WNND. Conclusions: Further studies are needed to understand the pathogenesis of WNND and to investigate the extent and the way the host inflammatory response either helps in controlling the infection or in worsening the outcomes. This might prove useful both for the development of target therapies and for the development of molecular markers allowing early identification of patients displaying an inflammatory response that puts them at a higher risk of developing neuroinvasive disease and who might thus benefit from early antiviral therapies.

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Signaling events evoked by domain III of envelop glycoprotein of tick-borne encephalitis virus and West Nile virus in human brain microvascular endothelial cells

Cited by 3 publications

References 110 publications

Differential transcriptome response of blood brain barrier spheroids to neuroinvasive Neisseria and Borrelia

Differential transcriptome response of blood brain barrier spheroids to neuroinvasive Neisseria and Borrelia

T Cells in Tick-Borne Flavivirus Encephalitis: A Review of Current Paradigms in Protection and Disease Pathology

Inflammatory Response Associated with West Nile Neuroinvasive Disease: A Systematic Review

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