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Review
. 2024 May 11;16(5):764.
doi: 10.3390/v16050764.

Intracellular Host Restriction of Hepatitis B Virus Replication

Affiliations
Review

Intracellular Host Restriction of Hepatitis B Virus Replication

Prakriti Sinha et al. Viruses. .

Abstract

The hepatitis B virus (HBV) infects hepatocytes and hijacks host cellular mechanisms for its replication. Host proteins can be frontline effectors of the cell's defense and restrict viral replication by impeding multiple steps during its intracellular lifecycle. This review summarizes many of the well-described restriction factors, their mechanisms of restriction, and counteractive measures of HBV, with a special focus on viral transcription. We discuss some of the limitations and knowledge gaps about the restriction factors, highlighting how these factors may be harnessed to facilitate therapeutic strategies against HBV.

Keywords: Smc5/6; cccDNA transcriptional silencing; hepatitis B virus; host restriction factors; viral transcription.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Host restriction factors inhibit distinct steps in the HBV life cycle. Hepatitis B virions bind the NTCP receptor and are endocytosed. After uncoating, rcDNA is transported into the nucleus. Once in the nucleus, rcDNA is repaired by host enzymes to form cccDNA. cccDNA is transcribed by host polymerases into the suite of viral RNAs that are translated into all viral proteins that are required for replication. In addition, pgRNA is transcribed from cccDNA: pgRNA is the template that is encapsidated in new virions along with HBV Pol. Reverse transcription of pgRNA results in rcDNA. Surface antigens embedded in the host TGN form the envelope of the nascent virion. The infectious virion is then secreted from the hepatocyte. Host factors that impede distinct steps in the viral lifecycle are shown in blue. The majority of host restriction factors that have been identified either diminish cccDNA-derived transcription or target already transcribed viral mRNAs, leading to their degradation.

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