Hepatitis B virus surface antigen and virion secretion pathway (HBV HBsAg/virion secretion pathway)

The Hepatitis B virus (HBV) surface antigen (HBsAg) and virion secretion pathway is a multi-step biological process essential for the propagation of HBV and the maintenance of chronic infection (Watanabe et al., 2007). In addition to infectious virions (Dane particles), HBV-infected hepatocytes secrete a vast excess of non-infectious subviral particles (SVPs) composed primarily of HBsAg. These SVPs function as an immunological decoy, exhausting the host's innate and adaptive immune responses and preventing the clearance of the virus (Rehermann & Nascimbeni, 2005). The secretion process utilizes host cellular machinery, including the endoplasmic reticulum-Golgi intermediate compartment and the endosomal sorting complex required for transport (ESCRT) pathway (Patient et al., 2009). Targeting this pathway with inhibitors, such as nucleic acid polymers (NAPs), aims to drastically reduce circulating HBsAg levels (Vaillant, 2016). This reduction is intended to 'unmask' the immune system, allowing for the restoration of host immune responses and the potential achievement of a functional cure, characterized by sustained HBsAg loss and undetectable HBV DNA (Cornberg et al., 2020).

Other names

HBsAg secretion pathwayHBV release pathwaySubviral particle secretion pathwayHBV egress pathwayHepatitis B virus assembly and secretion

Inhibition of the assembly and release of HBsAg-containing subviral particles and infectious virions from hepatocytes, typically by disrupting the interaction between HBsAg and host trafficking proteins such as HSP40 or components of the ESCRT machinery (Vaillant, 2016; Blanchet et al., 2015).