Revisiting Hepatitis B Virus: Challenges of Curative Therapies

Journal of Virology
Jianming HuAleem Siddiqui

Abstract

With a yearly death toll of 880,000, hepatitis B virus (HBV) remains a major health problem worldwide, despite an effective prophylactic vaccine and well-tolerated, effective antivirals. HBV causes chronic hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. The viral genome persists in infected hepatocytes even after long-term antiviral therapy, and its integration, though no longer able to support viral replication, destabilizes the host genome. HBV is a DNA virus that utilizes a virus-encoded reverse transcriptase to convert an RNA intermediate, termed pregenomic RNA, into the relaxed circular DNA genome, which is subsequently converted into a covalently closed circular DNA (cccDNA) in the host cell nucleus. cccDNA is maintained in the nucleus of the infected hepatocyte as a stable minichromosome and functions as the viral transcriptional template for the production of all viral gene products, and thus, it is the molecular basis of HBV persistence. The nuclear cccDNA pool can be replenished through recycling of newly synthesized, DNA-containing HBV capsids. Licensed antivirals target the HBV reverse transcriptase activity but fail to eliminate cccDNA, which would be required to cure HBV infection. Elimination of HBV...Continue Reading

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Citations

Jun 10, 2020·Cells·Mihaela-Olivia DobricaNorica Branza-Nichita
Aug 18, 2020·Cellular Microbiology·Anindita ChakrabortyJane A McKeating
May 13, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Geon-Woo KimAleem Siddiqui
Jan 5, 2021·Journal of Experimental & Clinical Cancer Research : CR·Wenbiao ChenHongyan Diao
Jun 26, 2020·Antiviral Research·Richard BoulonPatrick Labonté
Dec 1, 2020·Future Virology·Alexi Tallan, Zongdi Feng
Nov 6, 2020·Journal of Virology·Xupeng HongJianming Hu
Jan 6, 2021·Proceedings of the National Academy of Sciences of the United States of America·Geon-Woo Kim, Aleem Siddiqui
Sep 29, 2020·Journal of Hepatology·Sheng-Tao ChengJuan Chen
Dec 18, 2020·Frontiers in Cellular and Infection Microbiology·Hasan ImamAleem Siddiqui
Feb 6, 2021·Journal of Hepatocellular Carcinoma·Abdullah ElyPatrick Arbuthnot
Sep 1, 2020·Antiviral Research·Senko Tsukuda, Koichi Watashi

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