Hepatitis B surface antigen assembly and secretion machinery (HBsAg secretion machinery)

The Hepatitis B surface antigen (HBsAg) assembly and secretion machinery is a specialized pathway utilized by the Hepatitis B virus (HBV) to produce and release viral components (Vaillant, 2016, ACS Infect Dis). In addition to infectious virions, HBV-infected hepatocytes secrete a massive excess of non-infectious subviral particles (SVPs) composed of HBsAg (Blanchet et al., 2019, J Hepatol). These SVPs, which exist as spheres and filaments, circulate in the blood at concentrations up to 100,000 times higher than the actual virus (Vaillant, 2016, ACS Infect Dis). The primary biological role of this overproduction is to serve as an immunological decoy, exhausting the host's HBsAg-specific T-cells and neutralizing antibodies (Al-Mahtab et al., 2016, PLOS ONE). This process is a major driver of the immune tolerization observed in chronic hepatitis B (CHB) infections (Bazinet et al., 2017, Lancet Gastroenterol Hepatol). Targeting this machinery is a key therapeutic strategy aimed at achieving a functional cure by reducing the HBsAg burden (Vaillant, 2016, ACS Infect Dis). Nucleic acid polymers (NAPs) are the primary class of drugs designed to interact with this machinery, specifically blocking the assembly and release of SVPs (Blanchet et al., 2019, J Hepatol). By clearing circulating HBsAg, these inhibitors facilitate the restoration of the host immune response and increase the likelihood of seroconversion (Al-Mahtab et al., 2016, PLOS ONE).

Other names

HBV subviral particle assemblyHBsAg secretion pathwayHBV SVP secretionHepatitis B subviral particle secretion machinery

Inhibition of the assembly and release of non-infectious HBV subviral particles (SVPs) from hepatocytes into the circulation (Blanchet et al., 2019, J Hepatol).