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Journal of Virology, June 2003, p. 6466-6473, Vol. 77, No. 11
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.11.6466-6473.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Characterization of a Conformational Epitope on Hepatitis B Virus Core Antigen and Quasiequivalent Variations in Antibody Binding

J. F. Conway,1 N. R. Watts,2,3 D. M. Belnap,3 N. Cheng,3 S. J. Stahl,2 P. T. Wingfield,2 and A. C. Steven3*

Laboratoire de Microscopie Electronique, Institut de Biologie Structurale J.-P. Ebel, Grenoble 38027, France,1 Protein Expression Laboratory,2 Laboratory of Structural Biology, National Institute of Arthritis, Musculoskeletal, and Skin Diseases, National Institutes of Health, Bethesda, Maryland 208923

Received 19 November 2002/ Accepted 20 February 2003

We have characterized a conformational epitope on capsids of hepatitis B virus (HBV) by cryo-electron microscopy and three-dimensional image reconstruction of Fab-labeled capsids to ~10-Å resolution, combined with molecular modeling. The epitope straddles the interface between two adjacent subunits and is discontinuous, consisting of five peptides—two on one subunit and three on its neighbor. Together, the two icosahedral forms of the HBV capsid—T=3 and T=4 particles—present seven quasiequivalent variants of the epitope. Of these, only three bind this Fab. Occupancy ranges from ~100 to ~0%, reflecting conformational variations in the epitope and steric blocking effects. In the former, small shifts of the component peptides have large effects on binding affinity. This approach appears to hold general promise for elucidating conformational epitopes of HBV and other viruses, including those of neutralizing and diagnostic significance.

* Corresponding author. Mailing address: Bldg. 50, Rm. 1517, MSC 8025, National Institutes of Health, Bethesda, MD 20892-8025. Phone: (301) 496-0132. Fax: (301) 480-1191. E-mail: Alasdair_Steven{at}nih.gov.

Journal of Virology, June 2003, p. 6466-6473, Vol. 77, No. 11
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.11.6466-6473.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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