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

BACKGROUND: Tick-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 predi...

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Autores principales: Ignatieva, Elena V., Igoshin, Alexander V., Yudin, Nikolay S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751789/
https://www.ncbi.nlm.nih.gov/pubmed/29297316
http://dx.doi.org/10.1186/s12862-017-1107-8
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author Ignatieva, Elena V.
Igoshin, Alexander V.
Yudin, Nikolay S.
author_facet Ignatieva, Elena V.
Igoshin, Alexander V.
Yudin, Nikolay S.
author_sort Ignatieva, Elena V.
collection PubMed
description BACKGROUND: Tick-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. RESULTS: Based 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. CONCLUSIONS: A 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 MATERIAL: The online version of this article (10.1186/s12862-017-1107-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-57517892018-01-05 A database of human genes and a gene network involved in response to tick-borne encephalitis virus infection Ignatieva, Elena V. Igoshin, Alexander V. Yudin, Nikolay S. BMC Evol Biol Research BACKGROUND: Tick-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. RESULTS: Based 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. CONCLUSIONS: A 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 MATERIAL: The online version of this article (10.1186/s12862-017-1107-8) contains supplementary material, which is available to authorized users. BioMed Central 2017-12-28 /pmc/articles/PMC5751789/ /pubmed/29297316 http://dx.doi.org/10.1186/s12862-017-1107-8 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Ignatieva, Elena V.
Igoshin, Alexander V.
Yudin, Nikolay S.
A database of human genes and a gene network involved in response to tick-borne encephalitis virus infection
title A database of human genes and a gene network involved in response to tick-borne encephalitis virus infection
title_full A database of human genes and a gene network involved in response to tick-borne encephalitis virus infection
title_fullStr A database of human genes and a gene network involved in response to tick-borne encephalitis virus infection
title_full_unstemmed A database of human genes and a gene network involved in response to tick-borne encephalitis virus infection
title_short A database of human genes and a gene network involved in response to tick-borne encephalitis virus infection
title_sort database of human genes and a gene network involved in response to tick-borne encephalitis virus infection
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751789/
https://www.ncbi.nlm.nih.gov/pubmed/29297316
http://dx.doi.org/10.1186/s12862-017-1107-8
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