Apoptosis- and survival-related gene mRNA profile in peripheral blood leukocytes in children with acute EBV infectious mononucleosis

Acute EBV-associated mononucleosis develops mainly in children and in patients with functionally impaired immune system. Consequently, it may result in developing secondary immunodeficiency, neoplasms as well as diverse alterations in cell-mediated immune reaction. Despite extensively examining mole...

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Autores principales:	N. A. Sakharnov, O. V. Utkin, E. N. Filatova, D. I. Knyazev, N. B. Presnyakova
Formato:	article
Lenguaje:	RU
Publicado:	Sankt-Peterburg : NIIÈM imeni Pastera 2020
Materias:	ebv-infectious mononucleosis leukocytes mrna expression levels apoptotic and survival pathways Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/232caa8921274e5a8fb2786f7355d7a3
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spelling	oai:doaj.org-article:232caa8921274e5a8fb2786f7355d7a32021-11-22T07:09:53ZApoptosis- and survival-related gene mRNA profile in peripheral blood leukocytes in children with acute EBV infectious mononucleosis2220-76192313-739810.15789/2220-7619-2019-5-6-723-734https://doaj.org/article/232caa8921274e5a8fb2786f7355d7a32020-02-01T00:00:00Zhttps://www.iimmun.ru/iimm/article/view/925https://doaj.org/toc/2220-7619https://doaj.org/toc/2313-7398Acute EBV-associated mononucleosis develops mainly in children and in patients with functionally impaired immune system. Consequently, it may result in developing secondary immunodeficiency, neoplasms as well as diverse alterations in cell-mediated immune reaction. Despite extensively examining molecular mechanisms of EBV infection, it is also necessary seek for new molecular and genetic factors underlying pathogenesis of EBV-mediated mononucleosis and EBV-associated malignant cell transformation is necessary, which might be used in clinical practice to monitor clinical score as well as predictive parameters for EBV-associated complications such as immunocompromised conditions and neoplasms. Here, we proposed to use our splicing sensitive DNA microarrays to perform a comprehensive semi-quantitative mRNA expression analysis for major apoptosis- and survival-related signaling components in peripheral blood leukocytes collected from children with acute EBV infectious mononucleosis as well as during recovery period. Using such DNA microchips allowed to assess both total (denoted by Σ) and separate transcript expression resulting from alternative splicing. It was shown that the balance of mRNA levels in acute phase of EBV-infectious mononucleosis was shifted towards upregulated expression of anti-apoptotic factors and components of of NF-κB-linked pro-survival signaling able to profoundly augment apoptosis resistance. Moreover, some EBV-associated changes (BIM/BCL2L11-Σ, PUMA/ BBC3-NM_001127241, BID-Σ, CASP3-Σ, NFKB1-Σ, RELA-Σ) were in agreement with the data published before. In addition, we also found previously unknown changes in level of EBV-associated coding and noncoding transcripts (DCR1/ TNFRSF10C-NM_003841, DR5/TNFRSF10B-NR_027140, CASP6 beta/CASP6-NM_032992, CASP7-NM_033338). Analyzing their properties allowed to suggest that they play an important role in the pathogenesis of EBV-associated mononucleosis. However, at asymptomatic recovery stage, level of some mRNA expression was kept altered compared to healthy volunteers (DCR2/TNFRSF10D-NM_003840, CASP8-Σ, CASP3-Σ, BIM/BCL2L11-Σ, BCL2-NM_000633, MCL1-Σ, BCL-W/BCL2L2-Σ, BCL-XL/BCL2L1-NM_138578, BIRC2-NM_001166, XIAP-NM_001167, TRAF2-NM_021138, MAP3K14-Σ, NFKB1-Σ), which may point at postponed EBV-associated molecular consequences. On one hand, such changes may be due to long-lasting anti-EBV immune response, whereas, on the other hand, they might be influenced by EBV-associated factors facilitating virus persistence. Overall, we identified the molecular features predisposing to chronic course of EBV-infection. The data obtained further expand our understanding about the molecular pathogenetic mechanisms for EBV infectious mononucleosis.N. A. SakharnovO. V. UtkinE. N. FilatovaD. I. KnyazevN. B. PresnyakovaSankt-Peterburg : NIIÈM imeni Pasteraarticleebv-infectious mononucleosisleukocytesmrna expression levelsapoptotic and survival pathwaysInfectious and parasitic diseasesRC109-216RUInfekciâ i Immunitet, Vol 9, Iss 5-6, Pp 723-734 (2020)
institution	DOAJ
collection	DOAJ
language	RU
topic	ebv-infectious mononucleosis leukocytes mrna expression levels apoptotic and survival pathways Infectious and parasitic diseases RC109-216
spellingShingle	ebv-infectious mononucleosis leukocytes mrna expression levels apoptotic and survival pathways Infectious and parasitic diseases RC109-216 N. A. Sakharnov O. V. Utkin E. N. Filatova D. I. Knyazev N. B. Presnyakova Apoptosis- and survival-related gene mRNA profile in peripheral blood leukocytes in children with acute EBV infectious mononucleosis
description	Acute EBV-associated mononucleosis develops mainly in children and in patients with functionally impaired immune system. Consequently, it may result in developing secondary immunodeficiency, neoplasms as well as diverse alterations in cell-mediated immune reaction. Despite extensively examining molecular mechanisms of EBV infection, it is also necessary seek for new molecular and genetic factors underlying pathogenesis of EBV-mediated mononucleosis and EBV-associated malignant cell transformation is necessary, which might be used in clinical practice to monitor clinical score as well as predictive parameters for EBV-associated complications such as immunocompromised conditions and neoplasms. Here, we proposed to use our splicing sensitive DNA microarrays to perform a comprehensive semi-quantitative mRNA expression analysis for major apoptosis- and survival-related signaling components in peripheral blood leukocytes collected from children with acute EBV infectious mononucleosis as well as during recovery period. Using such DNA microchips allowed to assess both total (denoted by Σ) and separate transcript expression resulting from alternative splicing. It was shown that the balance of mRNA levels in acute phase of EBV-infectious mononucleosis was shifted towards upregulated expression of anti-apoptotic factors and components of of NF-κB-linked pro-survival signaling able to profoundly augment apoptosis resistance. Moreover, some EBV-associated changes (BIM/BCL2L11-Σ, PUMA/ BBC3-NM_001127241, BID-Σ, CASP3-Σ, NFKB1-Σ, RELA-Σ) were in agreement with the data published before. In addition, we also found previously unknown changes in level of EBV-associated coding and noncoding transcripts (DCR1/ TNFRSF10C-NM_003841, DR5/TNFRSF10B-NR_027140, CASP6 beta/CASP6-NM_032992, CASP7-NM_033338). Analyzing their properties allowed to suggest that they play an important role in the pathogenesis of EBV-associated mononucleosis. However, at asymptomatic recovery stage, level of some mRNA expression was kept altered compared to healthy volunteers (DCR2/TNFRSF10D-NM_003840, CASP8-Σ, CASP3-Σ, BIM/BCL2L11-Σ, BCL2-NM_000633, MCL1-Σ, BCL-W/BCL2L2-Σ, BCL-XL/BCL2L1-NM_138578, BIRC2-NM_001166, XIAP-NM_001167, TRAF2-NM_021138, MAP3K14-Σ, NFKB1-Σ), which may point at postponed EBV-associated molecular consequences. On one hand, such changes may be due to long-lasting anti-EBV immune response, whereas, on the other hand, they might be influenced by EBV-associated factors facilitating virus persistence. Overall, we identified the molecular features predisposing to chronic course of EBV-infection. The data obtained further expand our understanding about the molecular pathogenetic mechanisms for EBV infectious mononucleosis.
format	article
author	N. A. Sakharnov O. V. Utkin E. N. Filatova D. I. Knyazev N. B. Presnyakova
author_facet	N. A. Sakharnov O. V. Utkin E. N. Filatova D. I. Knyazev N. B. Presnyakova
author_sort	N. A. Sakharnov
title	Apoptosis- and survival-related gene mRNA profile in peripheral blood leukocytes in children with acute EBV infectious mononucleosis
title_short	Apoptosis- and survival-related gene mRNA profile in peripheral blood leukocytes in children with acute EBV infectious mononucleosis
title_full	Apoptosis- and survival-related gene mRNA profile in peripheral blood leukocytes in children with acute EBV infectious mononucleosis
title_fullStr	Apoptosis- and survival-related gene mRNA profile in peripheral blood leukocytes in children with acute EBV infectious mononucleosis
title_full_unstemmed	Apoptosis- and survival-related gene mRNA profile in peripheral blood leukocytes in children with acute EBV infectious mononucleosis
title_sort	apoptosis- and survival-related gene mrna profile in peripheral blood leukocytes in children with acute ebv infectious mononucleosis
publisher	Sankt-Peterburg : NIIÈM imeni Pastera
publishDate	2020
url	https://doaj.org/article/232caa8921274e5a8fb2786f7355d7a3
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Apoptosis- and survival-related gene mRNA profile in peripheral blood leukocytes in children with acute EBV infectious mononucleosis

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