Research Highlights: Master Regulatory Proteins of the Liver Play a Role in HBV Infection

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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.[1][2][3][4]
  • 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.[6]
  • Inside the nucleus of liver cell, viral genome forms into covalent closed circular DNA or cccDNA that is difficult to eradicate. [5]
  • 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.

Sources:

Zhuang, X., Forde, D., Tsukuda, S. et al. Circadian control of hepatitis B virus replication. Nat Commun 12, 1658 (2021). https://doi.org/10.1038/s41467-021-21821-0

[1] Ryu W (2017). Molecular Virology of Human Pathogenic Viruses. Academic Press. pp. 247–260. ISBN 978-0-12-800838-6.

[2] Hunt R (21 November 2007). “Hepatitis viruses”. University of Southern California, Department of Pathology and Microbiology. Retrieved 13 March 2008.

[3] http://www.ictv.global/report/hepadnaviridae

[4] Hassan MM, Li D, El-Deeb AS, Wolff RA, Bondy ML, Davila M, Abbruzzese JL (October 2008). “Association between hepatitis B virus and pancreatic cancer”. Journal of Clinical Oncology. 26 (28): 4557–62. doi:10.1200/JCO.2008.17.3526. PMC 2562875. PMID 18824707

[5] https://medical-dictionary.thefreedictionary.com/cccDNA

[6] Eller, C., Heydmann, L., Colpitts, C. C., Verrier, E. R., Schuster, C., & Baumert, T. F. (2018). The functional role of sodium taurocholate cotransporting polypeptide NTCP in the life cycle of hepatitis B, C and D viruses. Cellular and molecular life sciences : CMLS75(21), 3895–3905. https://doi.org/10.1007/s00018-018-2892-y

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