Pre-Senescence Induction in Hepatoma Cells Favors Hepatitis C Virus Replication and Can Be Used in Exploring Antiviral Potential of Histone Deacetylase Inhibitors.
Alsu Z MalikovaAnastasia S ShcherbakovaKonstantin A KonduktorovAnastasia S ZemskayaAlexandra A DalinaVladimir I PopenkoOlga G LeonovaAlexey V MorozovNikolay N KurochkinOlga A SmirnovaSergey N KochetkovMaxim V KozlovPublished in: International journal of molecular sciences (2021)
Recent evidence suggests that fibrotic liver injury in patients with chronic hepatitis C correlates with cellular senescence in damaged liver tissue. However, it is still unclear how senescence can affect replication of the hepatitis C virus (HCV). In this work, we report that an inhibitor of cyclin-dependent kinases 4/6, palbociclib, not only induced in hepatoma cells a pre-senescent cellular phenotype, including G1 arrest in the cell cycle, but also accelerated viral replicon multiplication. Importantly, suppression of HCV replication by direct acting antivirals (DAAs) was barely affected by pre-senescence induction, and vice versa, the antiviral activities of host-targeting agents (HTAs), such as inhibitors of human histone deacetylases (HDACi), produced a wide range of reactions-from a dramatic reduction to a noticeable increase. It is very likely that under conditions of the G1 arrest in the cell cycle, HDACi exhibit their actual antiviral potency, since their inherent anticancer activity that complicates the interpretation of test results is minimized.
Keyphrases
- cell cycle
- hepatitis c virus
- endothelial cells
- liver injury
- cell proliferation
- drug induced
- human immunodeficiency virus
- induced apoptosis
- dna damage
- high glucose
- histone deacetylase
- cell cycle arrest
- stress induced
- dna methylation
- systemic sclerosis
- signaling pathway
- oxidative stress
- cell death
- diabetic rats
- sars cov
- endoplasmic reticulum stress
- cancer therapy
- idiopathic pulmonary fibrosis
- climate change
- pluripotent stem cells