Hepatitis B surface antigen (HBsAg) production and release machinery (HBsAg production/release machinery)

The Hepatitis B surface antigen (HBsAg) production and release machinery refers to the integrated viral and host cellular processes involved in the synthesis, assembly, and secretion of HBsAg. In patients with chronic hepatitis B (CHB), HBsAg is produced in massive excess, often 1,000 to 100,000 times the amount of infectious virions, circulating primarily as non-infectious subviral particles (SVPs) (Vaillant, 2016, PubMed: 26894846). These particles act as an immunological decoy, exhausting the host's immune system and preventing the clearance of the virus (Rehermann & Nascimbeni, 2005, PubMed: 15661902). Therapeutic targeting of this machinery, such as through nucleic acid polymers (NAPs) that block HBsAg release or RNA interference (RNAi) and antisense oligonucleotides (ASOs) that inhibit HBsAg production, aims to reduce HBsAg levels to allow for immune reconstitution (Bazinet et al., 2020, PubMed: 32622731). Achieving a functional cure for HBV—defined as sustained HBsAg loss—is the primary goal of these interventions. By lowering the circulating HBsAg burden, these therapies aim to "unmask" the virus to the immune system and facilitate long-term viral control. This approach is distinct from traditional nucleos(t)ide analogues, which inhibit viral DNA replication but have little effect on HBsAg levels.

Other names

HBsAg secretion pathwayHBV subviral particle assembly and releaseHBsAg synthesis and export machineryHepatitis B surface antigen subviral particle production

Inhibition of the assembly and secretion of HBsAg subviral particles (SVPs) from hepatocytes and the degradation of viral mRNA transcripts to suppress HBsAg synthesis.