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

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Abstract

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.

About the authors

N. A. Sakharnov

Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology

Author for correspondence.
Email: saharnov@nniiem.ru
ORCID iD: 0000-0003-3965-2033
http://www.nniiem.ru

Nikolai A. Sakharnov – Researcher, Laboratory of Molecular Biology and Biotechnology

603950, Nizhny Novgorod, Malaya Yamskaya str., 71
Phone: +7 (831) 469-79-46 (office); +7 950 624-87-12 (mobile). Fax: +7 (831) 469-79-20 

Russian Federation

O. V. Utkin

Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology

Email: utkino2004@mail.ru
ORCID iD: 0000-0002-7571-525X

PhD (Biology), Head of the Laboratory of Molecular Biology and Biotechnology

Nizhny Novgorod

Russian Federation

E. N. Filatova

Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology

Email: filatova@nniiem.ru
ORCID iD: 0000-0002-6683-7191

PhD (Biology), Leading Researcher, Laboratory of Molecular Biology and Biotechnology

Nizhny Novgorod

Russian Federation

D. I. Knyazev

Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology

Email: Dmitry-Kn@yandex.ru
ORCID iD: 0000-0002-6880-7105

PhD (Biology), Senior Researcher, Laboratory of Molecular Biology and Biotechnology

Nizhny Novgorod

Russian Federation

E. A. Kulova

Privolzhsky Research Medical University of the Ministry of Health of the Russian Federation

Email: dr_kulova@mail.ru

PhD (Medicine), Associate Professor, Infectious Diseases Department

Nizhny Novgorod

Russian Federation

N. B. Presnyakova

Blokhina Nizhny Novgorod Scientific Research Institute of Epidemiology and Microbiology

Email: Presnyakova_nb@mail.ru
ORCID iD: 0000-0001-5257-6210

Researcher, Laboratory of Molecular Biology and Biotechnology

Nizhny Novgorod

Russian Federation

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Copyright (c) 2020 Sakharnov N.A., Utkin O.V., Filatova E.N., Knyazev D.I., Kulova E.A., Presnyakova N.B.

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