Cryo-electron microscopy of hepatitis B virions reveals variability in envelope capsid interactions.
Hepatitis B virus (HBV) is a major human pathogen causing about 750,000 deaths per year. The virion consists of a nucleocapsid and an envelope formed by lipids, and three integral membrane proteins. Although we have detailed structural insights into the organization of the HBV core, the arrangement of the envelope in virions and its interaction with the nucleocapsid is elusive. Here we show the ultrastructure of hepatitis B virions purified from patient serum. We identified two morphological phenotypes, which appear as compact and gapped particles with nucleocapsids in distinguishable conformations. The overall structures of these nucleocapsids resemble recombinant cores with two alpha-helical spikes per asymmetric unit. At the charged tips the spikes are contacted by defined protrusions of the envelope proteins, probably via electrostatic interactions. The HBV envelope in the two morphotypes is to some extent variable, but the surface proteins follow a general packing scheme with up to three surface protein dimers per asymmetric unit. The variability in the structure of the envelope indicates that the nucleocapsid does not firmly constrain the arrangement of the surface proteins, but provides a general template for the packing.
Seitz
Stefan
S
Department of Molecular Virology, Otto-Meyerhof-Zentrum (OMZ), University of Heidelberg, and Department of Medicine II, University Hospital Mannheim, Germany.
Urban
Stephan
S
Antoni
Christoph
C
Böttcher
Bettina
B
D000595:Amino Acid Sequence; D036022:Capsid Proteins / Q000378:metabolism* / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D006509:Hepatitis B / Q000821:virology; D006515:Hepatitis B virus / Q000378:metabolism / Q000648:ultrastructure*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D014758:Viral Core Proteins / Q000737:chemistry; D014759:Viral Envelope Proteins / Q000378:metabolism* / Q000648:ultrastructure*; D014771:Virion / Q000378:metabolism / Q000648:ultrastructure*
D036022:Capsid Proteins; D014758:Viral Core Proteins; D014759:Viral Envelope Proteins