Increased concentration of interferon lambda-3, interferon beta and interleukin-10 in the cerebrospinal fluid of patients with tick-borne encephalitis

Grygorczuk, Sambor; Parczewski, Miłosz; Moniuszko, Anna; Świerzbińska, Renata; Kondrusik, Maciej; Zajkowska, Joanna; Czupryna, Piotr; Dunaj, Justyna; Boroń-Kaczmarska, Anna; Pancewicz, Sławomir

doi:10.1016/j.cyto.2014.10.001

Cited by 23 publications

(22 citation statements)

References 42 publications

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“…IFNλs are among the most recently described cytokines, and have been reported to be important for the pathogenesis, treatment response and outcome of viral and non-viral hepatitis 35 36 . Our findings in MHE were consistent with data from a previous study which described an elevation of IFNλ3 in CSF from patients with tick-borne encephalitis 37 . Studies of IFNλs on HE are limited.…”

Section: Discussionsupporting

confidence: 92%

Cytokine levels contribute to the pathogenesis of minimal hepatic encephalopathy in patients with hepatocellular carcinoma via STAT3 activation

Jin

et al. 2016

Sci Rep

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Hepatocellular carcinoma (HCC) patients were grouped according to the degree of encephalopathy, with healthy volunteers as controls. We investigated clinical presentation, protein and mRNA expression of 14 cytokines, and activation of six STAT proteins, the downstream signaling mediators. Levels of all 14 cytokines were significantly elevated in HCC patients with clinical hepatic encephalopathy. Statistical analysis showed that levels of IL-1β, IL-6, IFNγ, IL-17α, IFNλ2 and IFNλ3 were correlated with minimal hepatic encephalopathy (MHE). Multivariate regression analysis identified serum IL-6, IFNλ3 and IL-17α as independent risk factors for MHE. Increased mRNA levels of IL-6 and IFNγ were associated with MHE. Among the STAT proteins examined, only STAT3 was elevated in MHE. Treatment with a STAT3 inhibitor protected neurons from cytokine-induced apoptosis in vitro. In conclusion, this study identified potential biomarkers for MHE in HCC. The cytokines investigated may induce neural apoptosis via STAT3 in the pathogenesis of MHE in HCC.

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Section: Discussionsupporting

confidence: 92%

Cytokine levels contribute to the pathogenesis of minimal hepatic encephalopathy in patients with hepatocellular carcinoma via STAT3 activation

Jin

et al. 2016

Sci Rep

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“…Moreover, it was found that T cells contribute significantly to neuronal damage in human TBE (63), supporting the notion that liberation of inflammatory mediators and recruitment of T cells may contribute to nerve cell dysfunction in human TBEV infection. Likewise, RANTES has been found to be elevated in the cerebrospinal fluid of TBE patients, implicating the impact of RANTES-mediated trafficking of T lymphocytes into the CNS (64). In the current study, we demonstrated that RANTES induced by TBEV NS5 could efficiently recruit CD4 + T cells.…”

Section: Discussionsupporting

confidence: 62%

Tick-Borne Encephalitis Virus Nonstructural Protein NS5 Induces RANTES Expression Dependent on the RNA-Dependent RNA Polymerase Activity

Zheng

Yang

Jiang

et al. 2018

The Journal of Immunology

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Tick-borne encephalitis virus (TBEV) is one of the flaviviruses that targets the CNS and causes encephalitis in humans. The mechanism of TBEV that causes CNS destruction remains unclear. It has been reported that RANTES-mediated migration of human blood monocytes and T lymphocytes is specifically induced in the brain of mice infected with TBEV, which causes ensuing neuroinflammation and may contribute to brain destruction. However, the viral components responsible for RANTES induction and the underlying mechanisms remain to be fully addressed. In this study, we demonstrate that the NS5, but not other viral proteins of TBEV, induces RANTES production in human glioblastoma cell lines and primary astrocytes. TBEV NS5 appears to activate the IFN regulatory factor 3 (IRF-3) signaling pathway in a manner dependent on RIG-I/MDA5, which leads to the nuclear translocation of IRF-3 to bind with RANTES promoter. Further studies reveal that the activity of RNA-dependent RNA polymerase (RdRP) but not the RNA cap methyltransferase is critical for TBEV NS5-induced RANTES expression, and this is likely due to RdRP-mediated synthesis of dsRNA. Additional data indicate that the residues at K359, D361, and D664 of TBEV NS5 are critical for RdRP activity and RANTES induction. Of note, NS5s from other flaviviruses, including Japanese encephalitis virus, West Nile virus, Zika virus, and dengue virus, can also induce RANTES expression, suggesting the significance of NS5-induced RANTES expression in flavivirus pathogenesis. Our findings provide a foundation for further understanding how flaviviruses cause neuroinflammation and a potential viral target for intervention.

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“…CD209 gene was also included into the Allelic variant dataset based on data reported in [ 13 ]. In this study it was revealed that the rs2287886 SNP in the CD209 promoter region (but not rs287886 that was annotated to CD209 gene by [ 46 ]), was associated with predisposition to severe forms of TBE in the Russian population.…”

Section: Resultsmentioning

confidence: 99%

“…One SNP (rs3775291 in the 4th exon of TLR3 ) and one 32-base-pair deletion (rs333) in CCR5 coding region (CCR5delta32) were studied in Lithuanian population [ 18 ]. In addition, two SNPs (rs12979860 in the first intron of IFNL4 and rs287886 the first intron of ARID1B ) were studied in the Polish population [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

“…It should be noted that according to [ 46 ], rs12979860 locus (located in the first intron of IFNL4 and upstream of IFNL3) was associated with IFNL3 expression. The second polymorphic locus rs287886 described in this report was found to be associated with IL10 expression [ 46 ]. These authors annotated the second polymorphic locus (rs287886) to CD209 gene located on 19 chromosome.…”

Section: Resultsmentioning

confidence: 99%

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A database of human genes and a gene network involved in response to tick-borne encephalitis virus infection

2017

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BackgroundTick-borne encephalitis is caused by the neurotropic, positive-sense RNA virus, tick-borne encephalitis virus (TBEV). TBEV infection can lead to a variety of clinical manifestations ranging from slight fever to severe neurological illness. Very little is known about genetic factors predisposing to severe forms of disease caused by TBEV. The aims of the study were to compile a catalog of human genes involved in response to TBEV infection and to rank genes from the catalog based on the number of neighbors in the network of pairwise interactions involving these genes and TBEV RNA or proteins.ResultsBased on manual review and curation of scientific publications a catalog comprising 140 human genes involved in response to TBEV infection was developed. To provide access to data on all genes, the TBEVhostDB web resource (http://icg.nsc.ru/TBEVHostDB/) was created. We reconstructed a network formed by pairwise interactions between TBEV virion itself, viral RNA and viral proteins and 140 genes/proteins from TBEVHostDB. Genes were ranked according to the number of interactions in the network. Two genes/proteins (CCR5 and IFNAR1) that had maximal number of interactions were revealed. It was found that the subnetworks formed by CCR5 and IFNAR1 and their neighbors were a fragments of two key pathways functioning during the course of tick-borne encephalitis: (1) the attenuation of interferon-I signaling pathway by the TBEV NS5 protein that targeted peptidase D; (2) proinflammation and tissue damage pathway triggered by chemokine receptor CCR5 interacting with CD4, CCL3, CCL4, CCL2. Among nine genes associated with severe forms of TBEV infection, three genes/proteins (CCR5, IL10, ARID1B) were found to have protein-protein interactions within the network, and two genes/proteins (IFNL3 and the IL10, that was just mentioned) were up- or down-regulated in response to TBEV infection. Based on this finding, potential mechanisms for participation of CCR5, IL10, ARID1B, and IFNL3 in the host response to TBEV infection were suggested.ConclusionsA database comprising 140 human genes involved in response to TBEV infection was compiled and the TBEVHostDB web resource, providing access to all genes was created. This is the first effort of integrating and unifying data on genetic factors that may predispose to severe forms of diseases caused by TBEV. The TBEVHostDB could potentially be used for assessment of risk factors for severe forms of tick-borne encephalitis and for the design of personalized pharmacological strategies for the treatment of TBEV infection.Electronic supplementary materialThe online version of this article (10.1186/s12862-017-1107-8) contains supplementary material, which is available to authorized users.

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Increased concentration of interferon lambda-3, interferon beta and interleukin-10 in the cerebrospinal fluid of patients with tick-borne encephalitis

Cited by 23 publications

References 42 publications

Cytokine levels contribute to the pathogenesis of minimal hepatic encephalopathy in patients with hepatocellular carcinoma via STAT3 activation

Cytokine levels contribute to the pathogenesis of minimal hepatic encephalopathy in patients with hepatocellular carcinoma via STAT3 activation

Tick-Borne Encephalitis Virus Nonstructural Protein NS5 Induces RANTES Expression Dependent on the RNA-Dependent RNA Polymerase Activity

A database of human genes and a gene network involved in response to tick-borne encephalitis virus infection

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