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
Google Scholar
Right arrow Articles by Salisse, J.
Right arrow Articles by Sureau, C.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Salisse, J.
Right arrow Articles by Sureau, C.

 Previous Article  |  Next Article 

Journal of Virology, September 2009, p. 9321-9328, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.00678-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

A Function Essential to Viral Entry Underlies the Hepatitis B Virus "a" Determinant{triangledown}

Jessica Salisse1 and Camille Sureau1,2*

Laboratoire de Virologie Moléculaire, INTS, 75739 Paris, France,1 Department of Virology and Immunology, Southwest Foundation for Biomedical Research, San Antonio, Texas 782282

Received 2 April 2009/ Accepted 22 June 2009

The hepatitis B virus (HBV) particles bear a receptor-binding site located in the pre-S1 domain of the large HBV envelope protein. Using the hepatitis delta virus (HDV) as a surrogate of HBV, a second infectivity determinant was recently identified in the envelope proteins antigenic loop (AGL), and its activity was shown to depend upon cysteine residues that are essential for the structure of the HBV immunodominant "a" determinant. Here, an alanine-scanning mutagenesis approach was used to precisely map the AGL infectivity determinant to a set of conserved residues, which are predicted to cluster together with cysteines in the AGL disulfide bridges network. Several substitutions suppressed both infectivity and the "a" determinant, whereas others were infectivity deficient with only a partial impact on antigenicity. Interestingly, G145R, a substitution often arising under immune pressure selection and detrimental to the "a" determinant, had no effect on infectivity. Altogether, these findings indicate that the AGL infectivity determinant is closely related to, yet separable from, the "a" determinant. Finally, a selection of HDV entry-deficient mutations were introduced at the surface of HBV virions and shown to also abrogate infection in the HBV model. Therefore, a function can at last be assigned to the orphan "a" determinant, the first-discovered marker of HBV infection. The characterization of the AGL functions at viral entry may lead to novel approaches in the development of antivirals against HBV.

* Corresponding author. Mailing address: Laboratoire de Virologie Moléculaire, Institut National de la Transfusion Sanguine, 6 Rue Alexandre-Cabanel, 75739 Paris, France. Phone: 33 1 44493056. Fax: 33 1 44493059. E-mail: csureau{at}ints.fr

{triangledown} Published ahead of print on 1 July 2009.

Journal of Virology, September 2009, p. 9321-9328, Vol. 83, No. 18
0022-538X/09/$08.00+0     doi:10.1128/JVI.00678-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Le Duff, Y., Blanchet, M., Sureau, C. (2009). The Pre-S1 and Antigenic Loop Infectivity Determinants of the Hepatitis B Virus Envelope Proteins Are Functionally Independent. J. Virol. 83: 12443-12451 [Abstract] [Full Text]  
  • Lepere-Douard, C., Trotard, M., Le Seyec, J., Gripon, P. (2009). The First Transmembrane Domain of the Hepatitis B Virus Large Envelope Protein Is Crucial for Infectivity. J. Virol. 83: 11819-11829 [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»