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. 1996 Sep;70(9):5807–5811. doi: 10.1128/jvi.70.9.5807-5811.1996

Epitopes exposed on hepatitis delta virus ribonucleoproteins.

V V Bichko 1, S M Lemon 1, J G Wang 1, S Hwang 1, M M Lai 1, J M Taylor 1
PMCID: PMC190595  PMID: 8709197

Abstract

A total of 17 antibodies, raised in several nonhuman species and specific for different regions on the delta antigen (delta Ag), were used to map, via immunoprecipitation, those domains exposed on the surface of the viral ribonucleoprotein (RNP). These studies showed that the domains for the nuclear localization signal and the C-terminal extension, unique to the large form of delta Ag, are exposed. Also exposed is the C-terminal region of the small form of delta Ag. In contrast, reactivity was not found with the coiled-coil domain needed for protein dimerization. When the hepatitis delta virus (HDV) RNA was released by treatment of viral RNP with vanadyl ribonucleoside complexes, no change in the pattern of delta Ag epitope presentation was detected, consistent with the interpretation that a multimeric protein structure persists in the absence of RNA. These RNP studies have implications not only for understanding of the process of HDV assembly but also for evaluation of the immune responses of an infected host to HDV replication.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bergmann K. F., Cote P. J., Moriarty A., Gerin J. L. Hepatitis delta antigen. Antigenic structure and humoral immune response. J Immunol. 1989 Dec 1;143(11):3714–3721. [PubMed] [Google Scholar]
  2. Bichko V., Netter H. J., Taylor J. Introduction of hepatitis delta virus into animal cell lines via cationic liposomes. J Virol. 1994 Aug;68(8):5247–5252. doi: 10.1128/jvi.68.8.5247-5252.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bichko V., Schödel F., Nassal M., Gren E., Berzinsh I., Borisova G., Miska S., Peterson D. L., Gren E., Pushko P. Epitopes recognized by antibodies to denatured core protein of hepatitis B virus. Mol Immunol. 1993 Feb;30(3):221–231. doi: 10.1016/0161-5890(93)90051-c. [DOI] [PubMed] [Google Scholar]
  4. Chang F. L., Chen P. J., Tu S. J., Wang C. J., Chen D. S. The large form of hepatitis delta antigen is crucial for assembly of hepatitis delta virus. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8490–8494. doi: 10.1073/pnas.88.19.8490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chao M., Hsieh S. Y., Taylor J. The antigen of hepatitis delta virus: examination of in vitro RNA-binding specificity. J Virol. 1991 Aug;65(8):4057–4062. doi: 10.1128/jvi.65.8.4057-4062.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fu T. B., Taylor J. The RNAs of hepatitis delta virus are copied by RNA polymerase II in nuclear homogenates. J Virol. 1993 Dec;67(12):6965–6972. doi: 10.1128/jvi.67.12.6965-6972.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hwang S. B., Lai M. M. A unique conformation at the carboxyl terminus of the small hepatitis delta antigen revealed by a specific monoclonal antibody. Virology. 1993 Apr;193(2):924–931. doi: 10.1006/viro.1993.1201. [DOI] [PubMed] [Google Scholar]
  8. Kuo M. Y., Chao M., Taylor J. Initiation of replication of the human hepatitis delta virus genome from cloned DNA: role of delta antigen. J Virol. 1989 May;63(5):1945–1950. doi: 10.1128/jvi.63.5.1945-1950.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kuroki K., Russnak R., Ganem D. Novel N-terminal amino acid sequence required for retention of a hepatitis B virus glycoprotein in the endoplasmic reticulum. Mol Cell Biol. 1989 Oct;9(10):4459–4466. doi: 10.1128/mcb.9.10.4459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  11. Lai M. M. The molecular biology of hepatitis delta virus. Annu Rev Biochem. 1995;64:259–286. doi: 10.1146/annurev.bi.64.070195.001355. [DOI] [PubMed] [Google Scholar]
  12. Lazinski D. W., Taylor J. M. Recent developments in hepatitis delta virus research. Adv Virus Res. 1994;43:187–231. doi: 10.1016/s0065-3527(08)60049-4. [DOI] [PubMed] [Google Scholar]
  13. Lazinski D. W., Taylor J. M. Relating structure to function in the hepatitis delta virus antigen. J Virol. 1993 May;67(5):2672–2680. doi: 10.1128/jvi.67.5.2672-2680.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lee C. Z., Chen P. J., Chen D. S. Large hepatitis delta antigen in packaging and replication inhibition: role of the carboxyl-terminal 19 amino acids and amino-terminal sequences. J Virol. 1995 Sep;69(9):5332–5336. doi: 10.1128/jvi.69.9.5332-5336.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lee C. Z., Lin J. H., Chao M., McKnight K., Lai M. M. RNA-binding activity of hepatitis delta antigen involves two arginine-rich motifs and is required for hepatitis delta virus RNA replication. J Virol. 1993 Apr;67(4):2221–2227. doi: 10.1128/jvi.67.4.2221-2227.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nakabayashi H., Taketa K., Miyano K., Yamane T., Sato J. Growth of human hepatoma cells lines with differentiated functions in chemically defined medium. Cancer Res. 1982 Sep;42(9):3858–3863. [PubMed] [Google Scholar]
  17. Netter H. J., Wu T. T., Bockol M., Cywinski A., Ryu W. S., Tennant B. C., Taylor J. M. Nucleotide sequence stability of the genome of hepatitis delta virus. J Virol. 1995 Mar;69(3):1687–1692. doi: 10.1128/jvi.69.3.1687-1692.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Poisson F., Baillou F., Dubois F., Janvier B., Roingeard P., Goudeau A. Immune response to synthetic peptides of hepatitis delta antigen. J Clin Microbiol. 1993 Sep;31(9):2343–2349. doi: 10.1128/jcm.31.9.2343-2349.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rozzelle J. E., Jr, Wang J. G., Wagner D. S., Erickson B. W., Lemon S. M. Self-association of a synthetic peptide from the N terminus of the hepatitis delta virus protein into an immunoreactive alpha-helical multimer. Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):382–386. doi: 10.1073/pnas.92.2.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ryu W. S., Bayer M., Taylor J. Assembly of hepatitis delta virus particles. J Virol. 1992 Apr;66(4):2310–2315. doi: 10.1128/jvi.66.4.2310-2315.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ryu W. S., Netter H. J., Bayer M., Taylor J. Ribonucleoprotein complexes of hepatitis delta virus. J Virol. 1993 Jun;67(6):3281–3287. doi: 10.1128/jvi.67.6.3281-3287.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Semiletov Iu A., Karpova V. A., Smirnov V. D., Viazov S. O. Lokalizatsiia immunodominantnogo saita v sostave antigena virusa gepatita del'ta s pomoshch'iu sinteticheskikh peptidov. Bioorg Khim. 1993 Mar;19(3):277–285. [PubMed] [Google Scholar]
  23. Wang J. G., Cullen J., Lemon S. M. Immunoblot analysis demonstrates that the large and small forms of hepatitis delta virus antigen have different C-terminal amino acid sequences. J Gen Virol. 1992 Jan;73(Pt 1):183–188. doi: 10.1099/0022-1317-73-1-183. [DOI] [PubMed] [Google Scholar]
  24. Wang J. G., Jansen R. W., Brown E. A., Lemon S. M. Immunogenic domains of hepatitis delta virus antigen: peptide mapping of epitopes recognized by human and woodchuck antibodies. J Virol. 1990 Mar;64(3):1108–1116. doi: 10.1128/jvi.64.3.1108-1116.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Wang J. G., Lemon S. M. Hepatitis delta virus antigen forms dimers and multimeric complexes in vivo. J Virol. 1993 Jan;67(1):446–454. doi: 10.1128/jvi.67.1.446-454.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Xia Y. P., Lai M. M. Oligomerization of hepatitis delta antigen is required for both the trans-activating and trans-dominant inhibitory activities of the delta antigen. J Virol. 1992 Nov;66(11):6641–6648. doi: 10.1128/jvi.66.11.6641-6648.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]

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