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
Google Scholar
Right arrow Articles by Lepère-Douard, C.
Right arrow Articles by Gripon, P.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lepère-Douard, C.
Right arrow Articles by Gripon, P.

 Previous Article  |  Next Article 

Journal of Virology, November 2009, p. 11819-11829, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01026-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

The First Transmembrane Domain of the Hepatitis B Virus Large Envelope Protein Is Crucial for Infectivity{triangledown}

Charlotte Lepère-Douard,1,2,3 Maud Trotard,1,2,3 Jacques Le Seyec,1,2,3 and Philippe Gripon1,2,3*

Institut National de la Santé Et de la Recherche Médicale, Unité 522, Rennes, France,1 Equipe Associée SERAIC 4427, Université de Rennes 1, Rennes, France,2 Université de Rennes 1, Génomique Fonctionnelle Agronomie et Santé IFR 140, Rennes, France3

Received 20 May 2009/ Accepted 29 August 2009

The early steps of the hepatitis B virus (HBV) life cycle are still poorly understood. Indeed, neither the virus receptor at the cell surface nor the mechanism by which nucleocapsids are delivered to the cytosol of infected cells has been identified. Extensive mutagenesis studies in pre-S1, pre-S2, and most of the S domain of envelope proteins revealed the presence of two regions essential for HBV infectivity: the 77 first residues of the pre-S1 domain and a conformational motif in the antigenic loop of the S domain. In addition, at the N-terminal extremity of the S domain, a putative fusion peptide, partially overlapping the first transmembrane (TM1) domain and preceded by a PEST sequence likely containing several proteolytic cleavage sites, was identified. Since no mutational analysis of these two motifs potentially implicated in the fusion process was performed, we decided to investigate the ability of viruses bearing contiguous deletions or substitutions in the putative fusion peptide and PEST sequence to infect HepaRG cells. By introducing the mutations either in the L and M proteins or in the S protein, we demonstrated the following: (i) that in the TM1 domain of the L protein, three hydrophobic clusters of four residues were necessary for infectivity; (ii) that the same clusters were critical for S protein expression; and, finally, (iii) that the PEST sequence was dispensable for both assembly and infection processes.

* Corresponding author. Mailing address: EA-Seraic 4427, Faculté de pharmacie, 2 Avenue du professeur Léon Bernard, 35000 Rennes, France. Phone: 33 2 2323 4878. Fax: 33 2 2323 4794. E-mail: philippe.gripon{at}univ-rennes1.fr

{triangledown} Published ahead of print on 9 September 2009.

Journal of Virology, November 2009, p. 11819-11829, Vol. 83, No. 22
0022-538X/09/$08.00+0     doi:10.1128/JVI.01026-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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