Native hepatitis B virions and capsids visualized by electron cryomicroscopy.
Hepatitis B virus (HBV) infects more than 350 million people, of which one million will die every year. The infectious virion is an enveloped capsid containing the viral polymerase and double-stranded DNA genome. The structure of the capsid assembled in vitro from expressed core protein has been studied intensively. However, little is known about the structure and assembly of native capsids present in infected cells, and even less is known about the structure of mature virions. We used electron cryomicroscopy (cryo-EM) and image analysis to examine HBV virions (Dane particles) isolated from patient serum and capsids positive and negative for HBV DNA isolated from the livers of transgenic mice. Both types of capsids assembled as icosahedral particles indistinguishable from previous image reconstructions of capsids. Likewise, the virions contained capsids with either T = 3 or T = 4 icosahedral symmetry. Projections extending from the lipid envelope were attributed to surface glycoproteins. Their packing was unexpectedly nonicosahedral but conformed to an ordered lattice. These structural features distinguish HBV from other enveloped viruses.
Dryden
Kelly A
KA
Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037.
Wieland
Stefan F
SF
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037.
Whitten-Bauer
Christina
C
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037.
Gerin
John L
JL
Division of Molecular Virology and Immunology, Department of Microbiology and Immunology, Georgetown University Medical Center, Rockville, Maryland 20850.
Chisari
Francis V
FV
Department of Molecular and Experimental Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037.
Yeager
Mark
M
Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037; Division of Cardiovascular Diseases, Scripps Clinic, 10666 North Torrey Pines Road, La Jolla, California 92037. Electronic address: yeager@scripps.edu.
D000818:Animals; D002213:Capsid / Q000737:chemistry / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D004279:DNA, Viral / Q000097:blood / Q000737:chemistry / Q000648:ultrastructure; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry / Q000648:ultrastructure; D006509:Hepatitis B / Q000097:blood / Q000401:mortality / Q000821:virology; D006515:Hepatitis B virus / Q000737:chemistry / Q000648:ultrastructure*; D006801:Humans; D021621:Imaging, Three-Dimensional; D008055:Lipids / Q000737:chemistry; D008099:Liver / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D014764:Viral Proteins / Q000097:blood / Q000737:chemistry / Q000648:ultrastructure; D019065:Virus Assembly
D004279:DNA, Viral; D008055:Lipids; D014764:Viral Proteins; D012321:DNA-Directed RNA Polymerases