Fig. 6. Morphogenesis, envelopment and secretion of HBV.

Nucleocapsids associated with newly synthesized, envelope polypeptides, S, M, and L, which would have been co- and post-translationally modified by N-glycosylations and glycan processing (L, M, S) and O-glycosylation (M), and myristolyation (L). M, and possibly L, are “folded” by Calnexin, and BiP. L, M and S are all heavily disulfide bonded, are use Protein Disulphide Isomerase (PDI) is their maturation. Numerous cell functions mediate vesicle transport. Subviral particles of oligomerized S bud in to the lumen of the ER-Golgi and are secreted out of the cell via constitutive secretory mechanisms. Envelopment of nucleocapsids, to form virions, probably occurs at the ER and then a Multi Vesicular Body (MVP). MVP derived exosomes containing enveloped virions are thought to fuse with plasma membranes and result in virion release in to the blood. Note that this occurs in a “polarized” hepatocyte, in which secretion of virions is through the basolateral side of the cell. Cellular functions mediating these steps are indicated in orange, research phase compounds that interfere with these steps are shown in pinkish red, with compounds that are clinical phase, or approved, in light blue. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)