Fig. 5. HBV RNA translation, capsid formation, encapsidation, reverse transcription and recycling of the nucleocapsid to the nucleus.

Five main species of HBV mRNA are translated in the cytoplasm in to the viral polypeptides precore (precursor of HBeAg, from the 3.5 kb precore mRNA), core and pol (from the 3.5 kb pgRNA), envelope polypeptides L (from the 2.4 kb mRNA), envelope polypeptide, M and S (from the 2.1 kb mRNA) and X from the 0.7 kb mRNA. Core rapidly dimerizes, is modified by phosphorylations, and cooperates with pol and pgRNA to form the nucleocapsid. Host factors modulate translation, phosphorylation, and even folding through chaperons of the viral functions. Encapsidated viral pgRNA is reverse transcribed, and nucleocapsids are either enveloped and secreted (see Fig. 6), or not enveloped and recycled to the nucleus, where they may then begin the cycle of cccDNA production, and transcription of new viral gene products. 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.)