A new study entitled “Restitution of gene expression and histone acetylation signatures altered by hepatitis B virus through antiviral microRNA-like molecules in non transformed murine hepatocytes” shows that the hepatitis B virus induces alterations in gene expression profiles and epigenetic signature of host hepatocytes, and that targeting the infection can partly rescue these changes. The findings could lead to new treatment approaches and improved patient outcomes. The study was published in the Clinical Epigenetics journal.
Viruses’ infection of host cells leads to alterations in cells’ gene expression profiles that ultimately impact their epigenomes. However, comprehensive studies of epigenetic alterations as well their dynamics upon antiviral treatment are lacking in the research community.
Here, the authors studied how hepatitis B virus (HBV) replication impacts on both host cell gene expression and epigenetic signature and how impaired replication alters these hepatic features. Specifically, the authors focused on the role of histone acetyltransferase (HAT) and histone deacetylase (HDAC) activities in hepatocytes HBV-negative and HBV-positive. They found that upon HBV infection, hepatocytes’ gene expression and chromatin landscape are altered, particularly with a global hypoacetylation increase in two histones, H2A.Z and H3K9. The enhanced hypoacetylation profile was traced to depend on the activity of sirtuins, a clad of proteins with deacylase activity. Notably, however, no other deacetylases were identified, such as class I/II histone deacetylases. The authors further investigated the epigenomic alterations and found that H2A.Z/H3K9 changes in acetylation profile led to global structural changes in the cells’ chromatin. These structural changes were partially reverted upon treatment with anti-HBV microRNA (miRNA)-like molecules, thus establishing that the alterations are actively induced by HBV infection.
While a Hepatitis B vaccine and a battery of HBV treatments currently exist, these new insights into how the infection can be optimally targeted could lead to improve therapies in the near future.