Overexpression of DNA-methyltransferases in persistency of cccDNA pool in chronic hepatitis B

  • Authors: Kostyushev DS1, Zueva AP1,2, Brezgin SA1,3, Lipatnikov AD1,4, Simirskii VN5, Glebe D6, Volchkova EV3, Shipulin GA1, Chulanov VP1,3
  • Affiliations:
    1. ФБУН «Центральный научно-исследовательский институт эпидемиологии» Роспотребнадзора
    2. ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова»
    3. ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России
    4. ФГБОУ ВО «Российский химико-технологический университет им. Д.И. Менделеева» Минобрнауки России
    5. ФГБУН «Институт биологии развития им. Н.К. Кольцова» РАН
    6. Гессенский университет им. Ю. Либиха
  • Issue: Vol 89, No 11 (2017)
  • Pages: 21-26
  • Section: Editorial
  • URL: https://journals.rcsi.science/0040-3660/article/view/32287
  • DOI: https://doi.org/10.17116/terarkh2017891121-26
  • ID: 32287

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Full Text

Abstract

Aim. To define the role of DNA-methyltransferases of type 1 and type 3A in hepatitis B viral cycle. Materials and methods. Human hepatoma cells HepG2 with stable expression of 1.1-mer HBV genome were transfected with vectors encoding DNA-methyltransferase 1 (DNMT1), DNA-methyltransferase 3A (DNMT3A) or were co-transfected with these vectors. Total HBV DNA copy number, relative expression of pregenomic RNA (pgRNA), S-protein-encoding RNA (S-RNA) and cccDNA were analyzed by quantitative and semi-quantitative real-time PCR-analysis with TaqMan probes for assessment of DNMTs-mediated effects on HBV. Results. DNMT1 and DNMT3A suppress HBV transcription and replication, though to different magnitude. cccDNA pool is enlarged statistically significantly ≈2-fold (P<0.005) after transfection of DNMT3A, but is unaltered under DNMT1 treatment. Conclusion. DNMT3A regulates the size of cccDNA pool and is important for persistency of HBV infection.

About the authors

D S Kostyushev

ФБУН «Центральный научно-исследовательский институт эпидемиологии» Роспотребнадзора

Москва, Россия

A P Zueva

ФБУН «Центральный научно-исследовательский институт эпидемиологии» Роспотребнадзора; ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова»

Москва, Россия

S A Brezgin

ФБУН «Центральный научно-исследовательский институт эпидемиологии» Роспотребнадзора; ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России

Москва, Россия

A D Lipatnikov

ФБУН «Центральный научно-исследовательский институт эпидемиологии» Роспотребнадзора; ФГБОУ ВО «Российский химико-технологический университет им. Д.И. Менделеева» Минобрнауки России

Москва, Россия

V N Simirskii

ФГБУН «Институт биологии развития им. Н.К. Кольцова» РАН

Москва, Россия

D Glebe

Гессенский университет им. Ю. Либиха

Гессен, Германия

E V Volchkova

ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России

Москва, Россия

G A Shipulin

ФБУН «Центральный научно-исследовательский институт эпидемиологии» Роспотребнадзора

Москва, Россия

V P Chulanov

ФБУН «Центральный научно-исследовательский институт эпидемиологии» Роспотребнадзора; ФГАОУ ВО «Первый МГМУ им. И.М. Сеченова» Минздрава России

Москва, Россия

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