Previous Article | Next Article 
Journal of Virology, March 1999, p. 2052-2057, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Infection Process of the Hepatitis B Virus Depends
on the Presence of a Defined Sequence in the Pre-S1 Domain
J.
Le Seyec,
P.
Chouteau,
I.
Cannie,
C.
Guguen-Guillouzo, and
P.
Gripon*
Unité de Recherches
Hépatologiques U 49, Institut National de la Santé et de la
Recherche Médicale, Hôpital de Pontchaillou, 35033 Rennes Cedex, France
Received 24 July 1998/Accepted 20 November 1998
During the life cycle of hepatitis B virus (HBV), the large
envelope protein (L) plays a pivotal role. Indeed, this polypeptide is
essential for viral assembly and probably for the infection process. By
performing mutagenesis experiments, we have previously excluded a
putative involvement of the pre-S2 domain of the L protein in viral
infectivity. In the present study, we have evaluated the role of the
pre-S1 region in HBV infection. For this purpose, 21 mutants of the L
protein were created. The entire pre-S1 domain was covered by
contiguous deletions of 5 amino acids. First, after transfection into
HepG2 cells, the efficient expression of both glycosylated and
unglycosylated L mutant proteins was verified. The secretion rate of
envelope proteins was modified positively or negatively by deletions,
indicating that the pre-S1 domain contains several regulating sequences
able to influence the surface protein secretion. The ability of mutant
proteins to support the production of virions was then studied. Only
the four C-terminal deletions, covering the 17 amino acids suspected to
interact with the cytoplasmic nucleocapsids, inhibited virion release.
Finally, the presence of the modified pre-S1 domain at the external
side of all secreted virions was confirmed, and their infectivity was assayed on normal human hepatocytes in primary culture. Only a short
sequence including amino acids 78 to 87 tolerates internal deletions
without affecting viral infectivity. These results confirm the
involvement of the L protein in the infection step and demonstrate that
the sequence between amino acids 3 and 77 is involved in this process.
*
Corresponding author. Mailing address: Unité de
Recherches Hépatologiques, INSERM U49, Hôpital de
Pontchaillou, 35033 Rennes Cedex, France. Phone: (33) 02 99 54 37 37. Fax: (33) 02 99 54 01 37. E-mail:
philippe.gripon{at}rennes.inserm.fr.
Journal of Virology, March 1999, p. 2052-2057, Vol. 73, No. 3
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Abou-Jaoude, G., Sureau, C.
(2007). Entry of Hepatitis Delta Virus Requires the Conserved Cysteine Residues of the Hepatitis B Virus Envelope Protein Antigenic Loop and Is Blocked by Inhibitors of Thiol-Disulfide Exchange. J. Virol.
81: 13057-13066
[Abstract]
[Full Text]
-
Lepere, C., Regeard, M., Le Seyec, J., Gripon, P.
(2007). The Translocation Motif of Hepatitis B Virus Envelope Proteins Is Dispensable for Infectivity. J. Virol.
81: 7816-7818
[Abstract]
[Full Text]
-
Blanchet, M., Sureau, C.
(2007). Infectivity Determinants of the Hepatitis B Virus Pre-S Domain Are Confined to the N-Terminal 75 Amino Acid Residues. J. Virol.
81: 5841-5849
[Abstract]
[Full Text]
-
Gudima, S., Meier, A., Dunbrack, R., Taylor, J., Bruss, V.
(2007). Two Potentially Important Elements of the Hepatitis B Virus Large Envelope Protein Are Dispensable for the Infectivity of Hepatitis Delta Virus. J. Virol.
81: 4343-4347
[Abstract]
[Full Text]
-
Blanchet, M., Sureau, C.
(2006). Analysis of the Cytosolic Domains of the Hepatitis B Virus Envelope Proteins for Their Function in Viral Particle Assembly and Infectivity. J. Virol.
80: 11935-11945
[Abstract]
[Full Text]
-
Lundin, M., Lindstrom, H., Gronwall, C., Persson, M. A. A.
(2006). Dual topology of the processed hepatitis C virus protein NS4B is influenced by the NS5A protein.. J. Gen. Virol.
87: 3263-3272
[Abstract]
[Full Text]
-
Tacke, F, Liedtke, C, Bocklage, S, Manns, M P, Trautwein, C
(2005). CREB/PKA sensitive signalling pathways activate and maintain expression levels of the hepatitis B virus pre-S2/S promoter. Gut
54: 1309-1317
[Abstract]
[Full Text]
-
Barrera, A., Guerra, B., Notvall, L., Lanford, R. E.
(2005). Mapping of the Hepatitis B Virus Pre-S1 Domain Involved in Receptor Recognition. J. Virol.
79: 9786-9798
[Abstract]
[Full Text]
-
Kluge, B., Schlager, M., Pairan, A., Bruss, V.
(2005). Determination of the Minimal Distance between the Matrix and Transmembrane Domains of the Large Hepatitis B Virus Envelope Protein. J. Virol.
79: 7918-7921
[Abstract]
[Full Text]
-
Grgacic, E. V. L., Anderson, D. A.
(2005). St, a Truncated Envelope Protein Derived from the S Protein of Duck Hepatitis B Virus, Acts as a Chaperone for the Folding of the Large Envelope Protein. J. Virol.
79: 5346-5352
[Abstract]
[Full Text]
-
Gripon, P., Cannie, I., Urban, S.
(2005). Efficient Inhibition of Hepatitis B Virus Infection by Acylated Peptides Derived from the Large Viral Surface Protein. J. Virol.
79: 1613-1622
[Abstract]
[Full Text]
-
Zajakina, A., Kozlovska, T., Bruvere, R., Aleksejeva, J., Pumpens, P., Garoff, H.
(2004). Translation of hepatitis B virus (HBV) surface proteins from the HBV pregenome and precore RNAs in Semliki Forest virus-driven expression. J. Gen. Virol.
85: 3343-3351
[Abstract]
[Full Text]
-
Barrera, A., Guerra, B., Lee, H., Lanford, R. E.
(2004). Analysis of Host Range Phenotypes of Primate Hepadnaviruses by In Vitro Infections of Hepatitis D Virus Pseudotypes. J. Virol.
78: 5233-5243
[Abstract]
[Full Text]
-
Schildgen, O., Roggendorf, M., Lu, M.
(2004). Identification of a glycosylation site in the woodchuck hepatitis virus preS2 protein and its role in protein trafficking. J. Gen. Virol.
85: 787-793
[Abstract]
[Full Text]
-
Ruvoletto, M. G., Tono, N., Carollo, D., Vilei, T., Trentin, L., Muraca, M., Marino, M., Gatta, A., Fassina, G., Pontisso, P.
(2004). Surface expression of squamous cell carcinoma antigen (SCCA) can be increased by the preS1(21-47) sequence of hepatitis B virus. J. Gen. Virol.
85: 621-624
[Abstract]
[Full Text]
-
Wang, H.-C., Wu, H.-C., Chen, C.-F., Fausto, N., Lei, H.-Y., Su, I.-J.
(2003). Different Types of Ground Glass Hepatocytes in Chronic Hepatitis B Virus Infection Contain Specific Pre-S Mutants that May Induce Endoplasmic Reticulum Stress. Am. J. Pathol.
163: 2441-2449
[Abstract]
[Full Text]
-
Glebe, D., Aliakbari, M., Krass, P., Knoop, E. V., Valerius, K. P., Gerlich, W. H.
(2003). Pre-S1 Antigen-Dependent Infection of Tupaia Hepatocyte Cultures with Human Hepatitis B Virus. J. Virol.
77: 9511-9521
[Abstract]
[Full Text]
-
Sureau, C., Fournier-Wirth, C., Maurel, P.
(2003). Role of N Glycosylation of Hepatitis B Virus Envelope Proteins in Morphogenesis and Infectivity of Hepatitis Delta Virus. J. Virol.
77: 5519-5523
[Abstract]
[Full Text]
-
Lambert, C., Prange, R.
(2003). Chaperone action in the posttranslational topological reorientation of the hepatitis B virus large envelope protein: Implications for translocational regulation. Proc. Natl. Acad. Sci. USA
100: 5199-5204
[Abstract]
[Full Text]
-
Gripon, P., Rumin, S., Urban, S., Le Seyec, J., Glaise, D., Cannie, I., Guyomard, C., Lucas, J., Trepo, C., Guguen-Guillouzo, C.
(2002). Infection of a human hepatoma cell line by hepatitis B virus. Proc. Natl. Acad. Sci. USA
99: 15655-15660
[Abstract]
[Full Text]
-
O'Malley, B., Lazinski, D.
(2002). A Hepatitis B Surface Antigen Mutant That Lacks the Antigenic Loop Region Can Self-Assemble and Interact with the Large Hepatitis Delta Antigen. J. Virol.
76: 10060-10063
[Abstract]
[Full Text]
-
Grgacic, E. V. L.
(2002). Identification of structural determinants of the first transmembrane domain of the small envelope protein of duck hepatitis B virus essential for particle morphogenesis. J. Gen. Virol.
83: 1635-1644
[Abstract]
[Full Text]
-
Sung, V. M.-H., Lai, M. M. C.
(2002). Murine Retroviral Pseudotype Virus Containing Hepatitis B Virus Large and Small Surface Antigens Confers Specific Tropism for Primary Human Hepatocytes: a Potential Liver-Specific Targeting System. J. Virol.
76: 912-917
[Abstract]
[Full Text]
-
Chouteau, P., Le Seyec, J., Cannie, I., Nassal, M., Guguen-Guillouzo, C., Gripon, P.
(2001). A Short N-Proximal Region in the Large Envelope Protein Harbors a Determinant That Contributes to the Species Specificity of Human Hepatitis B Virus. J. Virol.
75: 11565-11572
[Abstract]
[Full Text]
-
Hartmann-Stühler, C., Prange, R.
(2001). Hepatitis B Virus Large Envelope Protein Interacts with {gamma}2-Adaptin, a Clathrin Adaptor-Related Protein. J. Virol.
75: 5343-5351
[Abstract]
[Full Text]
-
Grgacic, E. V. L., Schaller, H.
(2000). A Metastable Form of the Large Envelope Protein of Duck Hepatitis B Virus: Low-pH Release Results in a Transition to a Hydrophobic, Potentially Fusogenic Conformation. J. Virol.
74: 5116-5122
[Abstract]
[Full Text]
-
Lambert, C., Prange, R.
(2001). Dual Topology of the Hepatitis B Virus Large Envelope Protein. DETERMINANTS INFLUENCING POST-TRANSLATIONAL PRE-S TRANSLOCATION. J. Biol. Chem.
276: 22265-22272
[Abstract]
[Full Text]