Silencing HBV transcription with SMC5/6: has a path been found?

Chronic hepatitis B virus (HBV) infection is maintained by the viral nuclear covalently closed circular DNA (cccDNA) that is the transcriptional template for HBV’s mRNAs. The cccDNA is durable during current therapies, but a functional cure for HBV infections will require stable, off-treatment silencing of any cccDNA remaining in the body after treatment cessation.1 The cccDNA is silenced naturally during infection by binding of the structural maintenance of chromosome 5/6 (SMC5/6) complex to the cccDNA, and HBV antagonises this silencing with the HBx protein that binds to SMC5/6 and triggers its proteasomal degradation.2 In Gut, Allweiss and Giersch et al3 explored what happens to HBV mRNA transcription during and after suppression of viral mRNA and antigen levels in HBV-infected chimeric mice carrying humanised livers. Suppressing all HBV mRNAs with a small interfering RNA (siRNA) or with pegylated interferon α (Peg-IFNα) increased SMC5/6 binding...
Source: Gut - Category: Gastroenterology Authors: Tags: Gut Commentary Source Type: research