Master Regulatory Proteins of the Liver Play a Role in HBV Infection
- Chronic hepatitis B virus or HBV is a DNA virus in the genus Orthohepadnavirus and causes the disease hepatitis B.
- HBV also causes cancer that does not have curative treatments.
- HBV infection is a worldwide health issue and causes more than 800,000 deaths per year.
- HBV uses the receptor sodium taurocholate co-transporting polypeptide or NTCP to gain entry into the host liver cell.
- Inside the nucleus of liver cell, viral genome forms into covalent closed circular DNA or cccDNA that is difficult to eradicate. 
- The liver transcriptome has master regulatory proteins called REV-ERB and circadian factors BMAL1/CLOCK however, the role of these master regulatory proteins in HBV replication is unknown.
- Researchers used a circadian cycling liver cell-model.
- Researchers demonstrated that REV-ERB regulates NTCP-dependent hepatitis B and delta virus particle entry.
- Importantly, activation of REV-ERB by drugs inhibits HBV infection in mice.
- Researchers also discovered that BMAL1 binds to HBV genome and promotes viral activity.
- Inhibition by drugs of BMAL1 reduces the level of pre-genomic RNA which is important in viral replication.
- This study highlights the role of REV-ERB and BMAL1 master regulatory proteins of the liver transcriptome in regulating HBV.
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