Inhibition of hepatitis B virus production associated with high levels of intracellular viral DNA intermediates in iron-depleted HepG2.2.15 cells
Abstract
Backgrounds/Aims: The effects of iron-depletion on hepatitis B virus (HBV) replication were examined in HepG2.2.15 cells.
Methods: Proliferating cells were iron-depleted with desferrioxamine (DFO), at 20 or 100 mM for 48 h. Levels of viral mRNAs, cytoplasmic DNA replicative intermediates and virion production were examined. A comparative study was performed with hydroxyurea, a speci®c inhibitor of ribonucleotide reductase.
Results: In desferrioxamine treated cells, virion production is dramatically decreased, while viral replicative intermediates accumulate in the cytoplasm. DFO, like hydroxyurea, blocks cell cycle progression in the G1/S transition or S phase with a corresponding 2-fold increase of viral mRNAs. As expected, hydroxyurea leads to a strong reduction of virion production associated with low levels of intracellular replicative intermediates.
Conclusions: These results strongly suggest that iron depletion affects the HBV life cycle indirectly through the cell cycle arrest and directly through the inhibition of the viral DNA secretion. They also indicate the need to re-evaluate with caution the iron depletion protocols on HBV infected patients since a decrease of viral markers in the serum following iron-depletion may not re¯ect a decrease of viral replicative forms, but on the contrary, could be associated with active viral DNA synthesis.
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BibTeX
@article{chouteau2026inhibition,
title = {{Inhibition of hepatitis B virus production associated with high levels of intracellular viral DNA intermediates in iron-depleted HepG2.2.15 cells}},
author = {Philippe Chouteau and Jacques Le Seyec and Bénédicte Saulier-Le Dréan and Isabelle Cannie and Pierre Brissot and Gérard Lescoat and Christiane Guguen-Guillouzo and Philippe Gripon},
journal = {Journal of Hepatology},
year = {2026},
month = sep,
doi = {10.1016/s0168-8278(00)00012-x},
url = {https://hal.science/hal-05670825v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Inhibition of hepatitis B virus production associated with high levels of intracellular viral DNA intermediates in iron-depleted HepG2.2.15 cells
AU - Philippe Chouteau
AU - Jacques Le Seyec
AU - Bénédicte Saulier-Le Dréan
AU - Isabelle Cannie
AU - Pierre Brissot
AU - Gérard Lescoat
AU - Christiane Guguen-Guillouzo
AU - Philippe Gripon
PY - 2026
DA - 2026/09/24
JO - Journal of Hepatology
DO - 10.1016/s0168-8278(00)00012-x
UR - https://hal.science/hal-05670825v1
AB - Backgrounds/Aims: The effects of iron-depletion on hepatitis B virus (HBV) replication were examined in HepG2.2.15 cells. Methods: Proliferating cells were iron-depleted with desferrioxamine (DFO), at 20 or 100 mM for 48 h. Levels of viral mRNAs, cytoplasmic DNA replicative intermediates and virion production were examined. A comparative study was performed with hydroxyurea, a speci®c inhibitor of ribonucleotide reductase. Results: In desferrioxamine treated cells, virion production is dramatically decreased, while viral replicative intermediates accumulate in the cytoplasm. DFO, like hydroxyurea, blocks cell cycle progression in the G1/S transition or S phase with a corresponding 2-fold increase of viral mRNAs. As expected, hydroxyurea leads to a strong reduction of virion production associated with low levels of intracellular replicative intermediates. Conclusions: These results strongly suggest that iron depletion affects the HBV life cycle indirectly through the cell cycle arrest and directly through the inhibition of the viral DNA secretion. They also indicate the need to re-evaluate with caution the iron depletion protocols on HBV infected patients since a decrease of viral markers in the serum following iron-depletion may not re¯ect a decrease of viral replicative forms, but on the contrary, could be associated with active viral DNA synthesis.
SN - 0168-8278
SN - 1600-0641
ER -