title: Hepatitis B virus subviral envelope particle morphogenesis and intracellular trafficking.
abstract: Hepatitis B virus (HBV) is unusual in that its surface proteins (small [S], medium, and large [L]) are not only incorporated into the virion envelope but they also bud into empty subviral particles in great excess over virions. The morphogenesis of these subviral envelope particles remains unclear, but the S protein is essential and sufficient for budding. We show here that, in contrast to the presumed model, the HBV subviral particle formed by the S protein self-assembles into branched filaments in the lumen of the endoplasmic reticulum (ER). These long filaments are then folded and bridged for packing into crystal-like structures, which are then transported by ER-derived vesicles to the ER-Golgi intermediate compartment (ERGIC). Within the ERGIC, they are unpacked and relaxed, and their size and shape probably limits further progression through the secretory pathway. Such progression requires their conversion into spherical particles, which occurred spontaneously during the purification of these filaments by affinity chromatography. Small branched filaments are also formed by the L protein in the ER lumen, but these filaments are not packed into transport vesicles. They are transported less efficiently to the ERGIC, potentially accounting for the retention of the L protein within cells. These findings shed light on an important step in the HBV infectious cycle, as the intracellular accumulation of HBV subviral filaments may be directly linked to viral pathogenesis.
authors.affiliation: Université François Rabelais, INSERM ERI 19, Laboratoire de Biologie Cellulaire, Faculté de Médecine de Tours, 10 boulevard Tonnellé, F-37032 Tours Cedex, France.
authors.forename: Romuald
authors.initials: R
authors.lastname: Patient
authors.forename: Christophe
authors.initials: C
authors.lastname: Hourioux
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Sizaret
authors.forename: Sylvie
authors.initials: S
authors.lastname: Trassard
authors.forename: Camille
authors.initials: C
authors.lastname: Sureau
authors.forename: Philippe
authors.initials: P
authors.lastname: Roingeard
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004721:Endoplasmic Reticulum / Q000821:virology; D006056:Golgi Apparatus / Q000821:virology; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000502:physiology* / Q000648:ultrastructure*; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D009024:Morphogenesis; D021381:Protein Transport; D022161:Transport Vesicles / Q000821:virology; D014759:Viral Envelope Proteins / Q000378:metabolism; D014771:Virion / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D006514:Hepatitis B Surface Antigens; C096362:L protein, hepatitis B virus; C118669:S envelope protein, hepatitis B virus; D014759:Viral Envelope Proteins