Expression analysis of apoptotic and survival genes in blood leukocytes of children with various forms of HHV-6 infection

Despite that human herpes virus type 6 (HHV-6) is extremely spread worldwide, molecular mechanisms of behind HHV-6 infection pathogenesis remain largely unexplored. No molecular markers were found linked to unfavorable course of HHV-6 infection which could allow to ease up selecting proper therapy a...

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Autores principales: N. A. Sakharnov, O. V. Utkin, E. N. Filatova, D. I. Knyazev, E. A. Kulova, N. B. Presnyakova
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Publicado: Sankt-Peterburg : NIIÈM imeni Pastera 2020
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Acceso en línea:https://doaj.org/article/a06bd0c2ad0d4c729dae578d7d97ed01
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spelling oai:doaj.org-article:a06bd0c2ad0d4c729dae578d7d97ed012021-11-22T07:09:54ZExpression analysis of apoptotic and survival genes in blood leukocytes of children with various forms of HHV-6 infection2220-76192313-739810.15789/2220-7619-EAO-1335https://doaj.org/article/a06bd0c2ad0d4c729dae578d7d97ed012020-05-01T00:00:00Zhttps://www.iimmun.ru/iimm/article/view/1335https://doaj.org/toc/2220-7619https://doaj.org/toc/2313-7398Despite that human herpes virus type 6 (HHV-6) is extremely spread worldwide, molecular mechanisms of behind HHV-6 infection pathogenesis remain largely unexplored. No molecular markers were found linked to unfavorable course of HHV-6 infection which could allow to ease up selecting proper therapy and preventing development of complications. The aim of the study was to analyze expression of apoptosis and survival-related genes in blood leukocytes from 7–17-year-old children upon various forms of HHV-6 infection. The analysis was carried out by using DNA microarrays developed by us allowing to assess changes in expression level both of individual mRNAs and total gene set (-Σ). It was shown that during the acute phase of HHV-6 infection mRNA level was shifted toward pro-apoptotic factors. In the convalescence phase, most altered mRNA levels returned to normal. We have identified a set of mRNAs and genes whose expression level was significantly changed in acute disease phase. According to available data, these factors play an important role in regulation of studied signaling pathways. In order to search for HHV-6-associated factors, which markedly affect disease pattern of severe herpesvirus mixed infection, we analyzed significant changes of mRNA and genes expression levels in patients with severe HHV-6+EBV+CMV mixed infection and EBV+CMV mixed infection of moderate severity compared with healthy donors. The levels of 5 mRNAs (FAF1-NM_007051, DAPK2-NM_014326, CASP8AP2-NM_001137667, CASP8-NM_033356, BTK-NM_001287345) and 3 genes (FAS-Σ, Puma/BBC3-Σ, ITCH-Σ) were significantly increased in severe mixed infection comorbid with HHV-6 (EBV+CMV+HHV-6) but without HHV-6 (EBV+CMV) compared with healthy donors. Most of detected factors belong to Fas-mediated apoptosis pathway, and may be considered as candidate prognostic development factors of severe herpes virus infection involving HHV-6. This study profoundly extends existing understanding on molecular pathogenesis of HHV-6 infection involving apoptosis and pro-survival signaling pathways. Marked changes of mRNA and gene levels most likely contributed to the pathogenesis of HHV-6 as well as severe HHV-6+EBV+CMV mixed infection.N. A. SakharnovO. V. UtkinE. N. FilatovaD. I. KnyazevE. A. KulovaN. B. PresnyakovaSankt-Peterburg : NIIÈM imeni Pasteraarticlehhv-6 infectionsevere hhv-6+ebv+cmv mixed infectionleukocytesmrna expressionsignaling pathwaysapoptosisInfectious and parasitic diseasesRC109-216RUInfekciâ i Immunitet, Vol 10, Iss 2, Pp 315-328 (2020)
institution DOAJ
collection DOAJ
language RU
topic hhv-6 infection
severe hhv-6+ebv+cmv mixed infection
leukocytes
mrna expression
signaling pathways
apoptosis
Infectious and parasitic diseases
RC109-216
spellingShingle hhv-6 infection
severe hhv-6+ebv+cmv mixed infection
leukocytes
mrna expression
signaling pathways
apoptosis
Infectious and parasitic diseases
RC109-216
N. A. Sakharnov
O. V. Utkin
E. N. Filatova
D. I. Knyazev
E. A. Kulova
N. B. Presnyakova
Expression analysis of apoptotic and survival genes in blood leukocytes of children with various forms of HHV-6 infection
description Despite that human herpes virus type 6 (HHV-6) is extremely spread worldwide, molecular mechanisms of behind HHV-6 infection pathogenesis remain largely unexplored. No molecular markers were found linked to unfavorable course of HHV-6 infection which could allow to ease up selecting proper therapy and preventing development of complications. The aim of the study was to analyze expression of apoptosis and survival-related genes in blood leukocytes from 7–17-year-old children upon various forms of HHV-6 infection. The analysis was carried out by using DNA microarrays developed by us allowing to assess changes in expression level both of individual mRNAs and total gene set (-Σ). It was shown that during the acute phase of HHV-6 infection mRNA level was shifted toward pro-apoptotic factors. In the convalescence phase, most altered mRNA levels returned to normal. We have identified a set of mRNAs and genes whose expression level was significantly changed in acute disease phase. According to available data, these factors play an important role in regulation of studied signaling pathways. In order to search for HHV-6-associated factors, which markedly affect disease pattern of severe herpesvirus mixed infection, we analyzed significant changes of mRNA and genes expression levels in patients with severe HHV-6+EBV+CMV mixed infection and EBV+CMV mixed infection of moderate severity compared with healthy donors. The levels of 5 mRNAs (FAF1-NM_007051, DAPK2-NM_014326, CASP8AP2-NM_001137667, CASP8-NM_033356, BTK-NM_001287345) and 3 genes (FAS-Σ, Puma/BBC3-Σ, ITCH-Σ) were significantly increased in severe mixed infection comorbid with HHV-6 (EBV+CMV+HHV-6) but without HHV-6 (EBV+CMV) compared with healthy donors. Most of detected factors belong to Fas-mediated apoptosis pathway, and may be considered as candidate prognostic development factors of severe herpes virus infection involving HHV-6. This study profoundly extends existing understanding on molecular pathogenesis of HHV-6 infection involving apoptosis and pro-survival signaling pathways. Marked changes of mRNA and gene levels most likely contributed to the pathogenesis of HHV-6 as well as severe HHV-6+EBV+CMV mixed infection.
format article
author N. A. Sakharnov
O. V. Utkin
E. N. Filatova
D. I. Knyazev
E. A. Kulova
N. B. Presnyakova
author_facet N. A. Sakharnov
O. V. Utkin
E. N. Filatova
D. I. Knyazev
E. A. Kulova
N. B. Presnyakova
author_sort N. A. Sakharnov
title Expression analysis of apoptotic and survival genes in blood leukocytes of children with various forms of HHV-6 infection
title_short Expression analysis of apoptotic and survival genes in blood leukocytes of children with various forms of HHV-6 infection
title_full Expression analysis of apoptotic and survival genes in blood leukocytes of children with various forms of HHV-6 infection
title_fullStr Expression analysis of apoptotic and survival genes in blood leukocytes of children with various forms of HHV-6 infection
title_full_unstemmed Expression analysis of apoptotic and survival genes in blood leukocytes of children with various forms of HHV-6 infection
title_sort expression analysis of apoptotic and survival genes in blood leukocytes of children with various forms of hhv-6 infection
publisher Sankt-Peterburg : NIIÈM imeni Pastera
publishDate 2020
url https://doaj.org/article/a06bd0c2ad0d4c729dae578d7d97ed01
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