Determining molecular and genetic markers for severe EBV-mononucleosis

Epstein—Barr virus (EBV) is one of the etiological agents causing infectious mononucleosis. A severe form of the disease can result in developing serious complications, which risk might also depend on the state of patient’s immune system. To date, no specific tests for assessing a risk of developing...

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Autores principales:	E. N. Filatova, N. A. Sakharnov, O. V. Utkin, E. A. Kulova
Formato:	article
Lenguaje:	RU
Publicado:	Sankt-Peterburg : NIIÈM imeni Pastera 2020
Materias:	epstein—barr virus infectious mononucleosis severe form complication gene expression apoptosis splicing dna-microarray Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/a5b11e8b85344399bf5f47c5a32da613
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spelling	oai:doaj.org-article:a5b11e8b85344399bf5f47c5a32da6132021-11-22T07:09:55ZDetermining molecular and genetic markers for severe EBV-mononucleosis2220-76192313-739810.15789/2220-7619-DMA-1271https://doaj.org/article/a5b11e8b85344399bf5f47c5a32da6132020-11-01T00:00:00Zhttps://www.iimmun.ru/iimm/article/view/1271https://doaj.org/toc/2220-7619https://doaj.org/toc/2313-7398Epstein—Barr virus (EBV) is one of the etiological agents causing infectious mononucleosis. A severe form of the disease can result in developing serious complications, which risk might also depend on the state of patient’s immune system. To date, no specific tests for assessing a risk of developing severe disease form are available. Our study was aimed at identifying molecular genetic markers of severe EBV-infectious mononucleosis (EBV-IM) in immunocompetent peripheral blood cells. Expression of 483 genes and gene transcripts regulating apoptosis, proliferation and differentiation of immunocompetent cells was measured in the peripheral blood leukocytes from patients with severe and moderate EBV-IM as well as apparently healthy donors. A DNA-microarray designed by us and subsequent data processing were carried out by using custom-made “MiDA” software. To identify markers of a severe form of the pathology, expression of each gene and transcript was compared in EBV-IM patients and apparently healthy donors. For each gene and transcript, the level of expression fold change and significance for binary classification were determined. Genes and transcripts, characterized by the maximum values of two determined parameters while comparing patients with severe infection and healthy donors, as well as patients with severe and moderate EBV-IM forms, were selected as markers of severe EBV-IM. Genes and transcripts with differed expression in patients with moderate EBV-IM and healthy donors, were excluded from the list of markers. In addition, sex- and age-linked markers with differed expression were excluded as well. The markers for severe EBV-IM consisted of apoptosis regulators (BCL2L11, BIRC3 genes and XIAP.NM_001167 transcript) and splicing factors (CELF6 gene and SF1.NM_201995 transcript). Compared with donors and patients with a moderate form of the disease, a decreased expression of BCL2L11, BIRC3 genes, transcripts SF1.NM_201995 and XIAP.NM_001167, as well as increased expression of the CELF6 gene were detected in the blood of patients with severe EBV-IM. The functional role of identified molecular markers suggests that severe EBV-IM is characterized by suppressed mitochondrial and activated TRAF-dependent apoptosis pathways in immunocompetent cells. The expression pattern for select markers is specific for severe EBV-MI, not associated with patient sex and age. Thus, study data may be used to develop specific tools for assessing a risk of developing complications of EBV mononucleosis.E. N. FilatovaN. A. SakharnovO. V. UtkinE. A. KulovaSankt-Peterburg : NIIÈM imeni Pasteraarticleepstein—barr virusinfectious mononucleosissevere formcomplicationgene expressionapoptosissplicingdna-microarrayInfectious and parasitic diseasesRC109-216RUInfekciâ i Immunitet, Vol 10, Iss 4, Pp 707-716 (2020)
institution	DOAJ
collection	DOAJ
language	RU
topic	epstein—barr virus infectious mononucleosis severe form complication gene expression apoptosis splicing dna-microarray Infectious and parasitic diseases RC109-216
spellingShingle	epstein—barr virus infectious mononucleosis severe form complication gene expression apoptosis splicing dna-microarray Infectious and parasitic diseases RC109-216 E. N. Filatova N. A. Sakharnov O. V. Utkin E. A. Kulova Determining molecular and genetic markers for severe EBV-mononucleosis
description	Epstein—Barr virus (EBV) is one of the etiological agents causing infectious mononucleosis. A severe form of the disease can result in developing serious complications, which risk might also depend on the state of patient’s immune system. To date, no specific tests for assessing a risk of developing severe disease form are available. Our study was aimed at identifying molecular genetic markers of severe EBV-infectious mononucleosis (EBV-IM) in immunocompetent peripheral blood cells. Expression of 483 genes and gene transcripts regulating apoptosis, proliferation and differentiation of immunocompetent cells was measured in the peripheral blood leukocytes from patients with severe and moderate EBV-IM as well as apparently healthy donors. A DNA-microarray designed by us and subsequent data processing were carried out by using custom-made “MiDA” software. To identify markers of a severe form of the pathology, expression of each gene and transcript was compared in EBV-IM patients and apparently healthy donors. For each gene and transcript, the level of expression fold change and significance for binary classification were determined. Genes and transcripts, characterized by the maximum values of two determined parameters while comparing patients with severe infection and healthy donors, as well as patients with severe and moderate EBV-IM forms, were selected as markers of severe EBV-IM. Genes and transcripts with differed expression in patients with moderate EBV-IM and healthy donors, were excluded from the list of markers. In addition, sex- and age-linked markers with differed expression were excluded as well. The markers for severe EBV-IM consisted of apoptosis regulators (BCL2L11, BIRC3 genes and XIAP.NM_001167 transcript) and splicing factors (CELF6 gene and SF1.NM_201995 transcript). Compared with donors and patients with a moderate form of the disease, a decreased expression of BCL2L11, BIRC3 genes, transcripts SF1.NM_201995 and XIAP.NM_001167, as well as increased expression of the CELF6 gene were detected in the blood of patients with severe EBV-IM. The functional role of identified molecular markers suggests that severe EBV-IM is characterized by suppressed mitochondrial and activated TRAF-dependent apoptosis pathways in immunocompetent cells. The expression pattern for select markers is specific for severe EBV-MI, not associated with patient sex and age. Thus, study data may be used to develop specific tools for assessing a risk of developing complications of EBV mononucleosis.
format	article
author	E. N. Filatova N. A. Sakharnov O. V. Utkin E. A. Kulova
author_facet	E. N. Filatova N. A. Sakharnov O. V. Utkin E. A. Kulova
author_sort	E. N. Filatova
title	Determining molecular and genetic markers for severe EBV-mononucleosis
title_short	Determining molecular and genetic markers for severe EBV-mononucleosis
title_full	Determining molecular and genetic markers for severe EBV-mononucleosis
title_fullStr	Determining molecular and genetic markers for severe EBV-mononucleosis
title_full_unstemmed	Determining molecular and genetic markers for severe EBV-mononucleosis
title_sort	determining molecular and genetic markers for severe ebv-mononucleosis
publisher	Sankt-Peterburg : NIIÈM imeni Pastera
publishDate	2020
url	https://doaj.org/article/a5b11e8b85344399bf5f47c5a32da613
work_keys_str_mv	AT enfilatova determiningmolecularandgeneticmarkersforsevereebvmononucleosis AT nasakharnov determiningmolecularandgeneticmarkersforsevereebvmononucleosis AT ovutkin determiningmolecularandgeneticmarkersforsevereebvmononucleosis AT eakulova determiningmolecularandgeneticmarkersforsevereebvmononucleosis
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Determining molecular and genetic markers for severe EBV-mononucleosis

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