NDLI: Neutralization epitope responsible for the hepatitis B virus subtype-specific protection in chimpanzees

Content Provider	PubMed Central
Author	Zhang, Pei Yu, Mei-ying W. Venable, Richard Alter, Harvey J. Shih, J. Wai-kou
Copyright Year	2006
Abstract	Neutralizing monoclonal antibody (BX-182) directed against the d determinant of hepatitis B virus (HBV) surface antigen protected chimpanzees from infection by HBV subtype adw but not by subtype ayw, as demonstrated by intravenously inoculating a mixture of the antibody with the respective subtype of the virus. To elucidate the mechanism underlying the subtype-specific protection, a combinatorial approach of screening random peptide phage libraries, bioinformatics, and structure analysis was used in this study to identify the neutralization epitope responsible for the observed protection. The epitope was mapped at the N terminus of the pre-S1 region of the hepatitis B surface antigen between residues 17 and 21, of which the residues Val-18/Pro-19 were critical for antibody binding. Alignment of amino acid sequences derived from diverse genetic variants of HBV revealed that the epitope was present in ad subtypes and in their corresponding genotypes A, B, C, F, and H. By contrast, this epitope was not found in a majority of ay subtypes or in genotypes D, E, and G, where the antigenic residues Val-18/Pro-19 within the epitope were replaced by Thr/Ser, Thr/Thr, or Ala/Ser, respectively, resulting in a drastic conformational change of the epitope. These data indicate that, by binding discriminately to the subtype “d” epitope in the pre-S1 region, neutralizing antibody BX-182 protects chimpanzees from HBV infection in a subtype-specific manner, suggesting a potential escape mechanism for HBV genetic variants.
Related Links	http://dx.doi.org/10.1073/pnas.0603316103
Ending Page	9219
Page Count	6
Starting Page	9214
File Format	PDF
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	24
Volume Number	103
Language	English
Publisher	National Academy of Sciences
Publisher Date	2006-06-13
Access Restriction	Open
Rights Holder	National Academy of Sciences
Subject Keyword	General Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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