title: Chaperones involved in hepatitis B virus morphogenesis.
abstract: Little is known about host cell factors necessary for hepatitis B virus (HBV) assembly which involves envelopment of cytosolic nucleocapsids by the S, M and L transmembrane viral envelope proteins and subsequent budding into intraluminal cisternae. Central to virogenesis is the L protein that mediates hepatocyte receptor binding and envelopment of capsids. To serve these topologically conflicting roles, L protein exhibits an unusual dual membrane topology, disposing its N-terminal preS domain inside and outside of the virion lipid envelope. The mixed topology is achieved by posttranslational preS translocation of about half of the L protein molecules across a post-endoplasmic reticulum membrane. Here we identify and characterize a preS-specific sequence that confers the suppression of cotranslational translocation even of a model reporter. This cytosolic anchorage sequence specifically binds the cognate heat shock protein Hsc70, thus indicating chaperone participitation in HBV morphogenesis. Conversely, the M envelope protein needs the assistance of the chaperone calnexin for proper folding and trafficking. Calnexin selectively binds to the N-glycan, specific for M, rather than to the N-glycan, common to all three envelope proteins. As inhibition of the calnexin-M interaction blocks the secretion of viral envelopes, we propose an essential role for calnexin, as well as for Hsc70, in chaperoning HBV assembly.
authors.affiliation: Institute for Medical Microbiology and Hygiene, Johannes-Gutenberg-Universität Mainz, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Prange
authors.forename: M
authors.initials: M
authors.lastname: Werr
authors.forename: H
authors.initials: H
authors.lastname: Löffler-Mary
mesh_terms: D000818:Animals; D001692:Biological Transport; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000378:metabolism; D037281:Calnexin; D002352:Carrier Proteins / Q000378:metabolism*; D003600:Cytosol; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis / Q000235:genetics; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism*; D009024:Morphogenesis; D014176:Protein Biosynthesis; D017510:Protein Folding; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000378:metabolism
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; D006514:Hepatitis B Surface Antigens; C096362:L protein, hepatitis B virus; D018832:Molecular Chaperones; D011498:Protein Precursors; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; C050806:presurface protein 1, hepatitis B surface antigen; C050807:presurface protein 2, hepatitis B surface antigen; D037281:Calnexin