Virology: viral replication, current therapy and progress to a cure

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  • Hepatitis B virus (HBV) can cause persistent infection by the establishment of a viral covalently closed circular DNA (cccDNA), which forms a stable minichromosome in the hepatocyte nucleus.
  • In chronic hepatitis B, the cccDNA is largely refractory to elimination by the immune response or by nucleos(t)ide analogue (NA) therapy. Upon immunosuppression or cessation of therapy, the cccDNA can re-initiate virus replication, leading to reactivation of disease.
  • HBV has an unusual replication strategy; it employs an error-prone reverse transcription step that allows mutations to be generated. Recent research efforts have identified several new targets for therapeutic intervention which may lead to a functional cure.
  • HBV genotypes A-D are found worldwide; genotypes B and C are the major forms in Oceania and Asia. Different genotypes are associated with different rates of disease progression and risk of HCC (1).

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