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[How Histone Deacetylase 3 Controls Hepcidin Expression and Hepatitis C Virus Replication]
A S Shcherbakova1, S N Kochetkov1, M V Kozlov1,2
1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia.
Insights
Histone deacetylases (HDAC) regulate the hepatitis C virus (HCV) response by controlling hepcidin gene (HAMP) expression. This epigenetic interaction impacts iron metabolism during chronic HCV infection.
Area of Science:
- Virology
- Epigenetics
- Hepatology
Background:
- Histone deacetylases (HDAC) play a critical role in regulating cellular responses to Hepatitis C Virus (HCV) infection.
- Chronic HCV infection in liver tissues is associated with reduced hepcidin gene (HAMP) expression, a key regulator of iron export.
- Oxidative stress induced by HCV infection contributes to the downregulation of HAMP expression in hepatocytes.
Conclusions:
- The interplay between HCV, HDAC3, STAT3, and HAMP is crucial for understanding iron metabolism dysregulation in chronic hepatitis C.
- Epigenetic modifications, particularly histone acetylation, are central to the host's response to HCV infection.
- Targeting this epigenetic regulatory circuit may offer novel therapeutic strategies for managing chronic HCV infection and associated liver disease.
Abstract:
The key role of histone deacetylases (HDAC) in the regulation of the cellular response to infection with the hepatitis C virus (HCV) was first demonstrated in 2008. When studying the metabolism of iron in the liver tissues of patients with chronic hepatitis C, the authors found that the expression of the hepcidin gene (HAMP), a hormone regulator of iron export, is markedly reduced in hepatocytes under conditions of oxidative stress caused by viral infection. HDAC were involved in the regulation of hepcidin expression through the control of acetylation level of histones and transcription factors, primarily STAT3, associated with the HAMP promoter. The purpose of this review was to summarize current data on the functioning of the HCV-HDAC3-STAT3-HAMP regulatory circuit as an example of a well-characterized interaction between the virus and the epigenetic apparatus of the host cell.
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