This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yuan, T. T.-T.
Right arrow Articles by Shih, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yuan, T. T.-T.
Right arrow Articles by Shih, C.

 Previous Article  |  Next Article 

Journal of Virology, July 1999, p. 5731-5740, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

The Mechanism of an Immature Secretion Phenotype of a Highly Frequent Naturally Occurring Missense Mutation at Codon 97 of Human Hepatitis B Virus Core Antigen

Thomas Ta-Tung Yuan, Gautam Kumar Sahu, William E. Whitehead, Richard Greenberg, and Chiaho Shih*

Departments of Pathology and of Microbiology and Immunology, Center for Tropical Diseases, University of Texas Medical Branch, Galveston, Texas 77555-0609

Received 10 December 1998/Accepted 29 March 1999

A very frequent missense mutation at codon 97 of human hepatitis B virus (HBV) core antigen (HBcAg) has been found in chronic carriers worldwide. Functional characterization of this mutant revealed one intracellular and two extracellular phenotypes in contrast to wild-type HBV: (i) a 6- to 12-fold decrease in the level of the full-length relaxed circular DNA, a 4- to 5-fold decrease in the plus-strand DNA, and an approximately 1.8-fold decrease in the minus-strand and overall DNA levels in the intracellular viral core particles; (ii) a 5.7-fold increase in the immature secretion of Dane particles, containing minus-strand, single-stranded virion DNA; and (iii) a significant reduction of nonenveloped core particles in the medium. The steady-state levels of mutant and wild-type core proteins expressed from the same vector appeared to be similar. Using a complementation assay and gradient centrifugation analysis, we demonstrated that this mutant core protein alone is necessary and sufficient for immature secretion. The decreased level of intracellular HBV DNA is caused by both the cis defect of the mutant genome and the trans defect of the mutant core protein. We have dissected further the relationship between the intracellular and extracellular phenotypes of mutant F97L. The pleiotropic effects of the HBcAg codon 97 mutation were observed consistently in several different experimental settings. The mechanism and biological significance of these findings are discussed.

* Corresponding author. Mailing address: Department of Pathology, Center for Tropical Diseases, University of Texas Medical Branch, Galveston, TX 77555-0609. Phone: (409) 772-2563. Fax: (409) 747-2429. E-mail: cshih{at}utmb.edu.

Journal of Virology, July 1999, p. 5731-5740, Vol. 73, No. 7
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Newman, M., Chua, P. K., Tang, F.-M., Su, P.-Y., Shih, C. (2009). Testing an Electrostatic Interaction Hypothesis of Hepatitis B Virus Capsid Stability by Using an In Vitro Capsid Disassembly/Reassembly System. J. Virol. 83: 10616-10626 [Abstract] [Full Text]  
  • Garcia, M. L., Byfield, R., Robek, M. D. (2009). Hepatitis B Virus Replication and Release Are Independent of Core Lysine Ubiquitination. J. Virol. 83: 4923-4933 [Abstract] [Full Text]  
  • Schormann, W., Kraft, A., Ponsel, D., Bruss, V. (2006). Hepatitis B virus particle formation in the absence of pregenomic RNA and reverse transcriptase.. J. Virol. 80: 4187-4190 [Abstract] [Full Text]  
  • Chua, P. K., Wang, R. Y.-L., Lin, M.-H., Masuda, T., Suk, F.-M., Shih, C. (2005). Reduced Secretion of Virions and Hepatitis B Virus (HBV) Surface Antigen of a Naturally Occurring HBV Variant Correlates with the Accumulation of the Small S Envelope Protein in the Endoplasmic Reticulum and Golgi Apparatus. J. Virol. 79: 13483-13496 [Abstract] [Full Text]  
  • Perlman, D. H., Berg, E. A., O'Connor, P. B., Costello, C. E., Hu, J. (2005). Reverse transcription-associated dephosphorylation of hepadnavirus nucleocapsids. Proc. Natl. Acad. Sci. USA 102: 9020-9025 [Abstract] [Full Text]  
  • Le Pogam, S., Chua, P. K., Newman, M., Shih, C. (2005). Exposure of RNA Templates and Encapsidation of Spliced Viral RNA Are Influenced by the Arginine-Rich Domain of Human Hepatitis B Virus Core Antigen (HBcAg 165-173). J. Virol. 79: 1871-1887 [Abstract] [Full Text]  
  • Ning, B., Shih, C. (2004). Nucleolar Localization of Human Hepatitis B Virus Capsid Protein. J. Virol. 78: 13653-13668 [Abstract] [Full Text]  
  • Ceres, P., Stray, S. J., Zlotnick, A. (2004). Hepatitis B Virus Capsid Assembly Is Enhanced by Naturally Occurring Mutation F97L. J. Virol. 78: 9538-9543 [Abstract] [Full Text]  
  • Khan, N., Guarnieri, M., Ahn, S. H., Li, J., Zhou, Y., Bang, G., Kim, K.-H., Wands, J. R., Tong, S. (2004). Modulation of Hepatitis B Virus Secretion by Naturally Occurring Mutations in the S Gene. J. Virol. 78: 3262-3270 [Abstract] [Full Text]  
  • Newman, M., Suk, F.-M., Cajimat, M., Chua, P. K., Shih, C. (2003). Stability and Morphology Comparisons of Self-Assembled Virus-Like Particles from Wild-Type and Mutant Human Hepatitis B Virus Capsid Proteins. J. Virol. 77: 12950-12960 [Abstract] [Full Text]  
  • Chua, P. K., Wen, Y.-M., Shih, C. (2003). Coexistence of Two Distinct Secretion Mutations (P5T and I97L) in Hepatitis B Virus Core Produces a Wild-Type Pattern of Secretion. J. Virol. 77: 7673-7676 [Abstract] [Full Text]  
  • Parekh, S., Zoulim, F., Ahn, S. H., Tsai, A., Li, J., Kawai, S., Khan, N., Trepo, C., Wands, J., Tong, S. (2003). Genome Replication, Virion Secretion, and e Antigen Expression of Naturally Occurring Hepatitis B Virus Core Promoter Mutants. J. Virol. 77: 6601-6612 [Abstract] [Full Text]  
  • Perlman, D., Hu, J. (2003). Duck Hepatitis B Virus Virion Secretion Requires a Double-Stranded DNA Genome. J. Virol. 77: 2287-2294 [Abstract] [Full Text]  
  • Suk, F.-M., Lin, M.-H., Newman, M., Pan, S., Chen, S.-H., Liu, J.-D., Shih, C. (2002). Replication Advantage and Host Factor-Independent Phenotypes Attributable to a Common Naturally Occurring Capsid Mutation (I97L) in Human Hepatitis B Virus. J. Virol. 76: 12069-12077 [Abstract] [Full Text]  
  • Le Pogam, S., Shih, C. (2002). Influence of a Putative Intermolecular Interaction between Core and the Pre-S1 Domain of the Large Envelope Protein on Hepatitis B Virus Secretion. J. Virol. 76: 6510-6517 [Abstract] [Full Text]  
  • Le Pogam, S., Yuan, T. T.-T., Sahu, G. K., Chatterjee, S., Shih, C. (2000). Low-Level Secretion of Human Hepatitis B Virus Virions Caused by Two Independent, Naturally Occurring Mutations (P5T and L60V) in the Capsid Protein. J. Virol. 74: 9099-9105 [Abstract] [Full Text]  
  • Yuan, T. T.-T., Shih, C. (2000). A Frequent, Naturally Occurring Mutation (P130T) of Human Hepatitis B Virus Core Antigen Is Compensatory for Immature Secretion Phenotype of Another Frequent Variant (I97L). J. Virol. 74: 4929-4932 [Abstract] [Full Text]  
  • Yuan, T. T.-T., Tai, P.-C., Shih, C. (1999). Subtype-Independent Immature Secretion and Subtype-Dependent Replication Deficiency of a Highly Frequent, Naturally Occurring Mutation of Human Hepatitis B Virus Core Antigen. J. Virol. 73: 10122-10128 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»