Morphogenesis of the hepatitis B virion and subviral particles in the liver of transgenic mice

Up to date, no ultrastructure showing the HBV budding site has ever been reported. In this study, the liver of transgenic mice expressing a high titer of HBV was processed for cryo-ultrathin section electron microscopy. This approach preserves membrane structures very well and thus allowed us to find HBV (Dane particles) and subviral particles (spherical and filamentous form) present separately inside the lumen of the endoplasmic reticulum (ER). Envelopment of single core particle by the ER was found near the Golgi region and mature Dane particles usually resided singularly in a 70–90 nm vesicle at the end of ER or near to mitochondria. Filamentous particles, either in an array or as a single filament inside various sizes of vesicles, were most frequently; these particles were found adjacent to the Golgi region or bile canaliculi. The formation of 22-nm spherical particles seems to occur inside the ER by a transition from preformed filaments to a structure similar to beads on a string. This study is the first report to demonstrate a serial process by which hepatitis B virion assembly takes place in the ER region and distinguishes two separate routes for the morphogenesis of virions and subviral particles.