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J Virol, July 1998, p. 5573-5578, Vol. 72, No. 7
Unité de Recherches
Hépatologiques U 49, Institut National de la Santé et de
la Recherche Médicale, Hôpital de Pontchaillou, 35033 Rennes Cedex, France
Received 28 October 1997/Accepted 18 March 1998
Among the three viral proteins present in the hepatitis B virus
(HBV) envelope, both the small and large polypeptides, but not the
middle polypeptide, are necessary for the production of complete viral
particles. Whereas it has been established that the C-terminal
extremity of the pre-S1 region is required for HBV morphogenesis,
whether the pre-S2 region of the large surface protein plays a critical
role remains questionable. In the present study, we have analyzed the
role of the large-polypeptide pre-S2 region in viral maturation and
infectivity. For this purpose, mutants bearing contiguous deletions
covering the entire pre-S2 domain were generated. First, the efficient
expression of all the mutant large envelope proteins was verified and
their ability to substitute for the wild-type form in virion secretion
was tested. We found that distinct deletions covering the domain
between amino acids 114 and 163 still allowed virion production. In
contrast, the polypeptide lacking the first 5 amino acids of pre-S2
(amino acids 109 to 113) was unable to support viral secretion. This result shows that the domain of the large surface protein, required for
this process, must be extended to the N-terminal extremity of pre-S2.
We then demonstrated that all the mutants competent for virion release
were able to infect normal human hepatocytes in primary culture. Taken
together, these results indicate that only 10% of the large-protein
pre-S2 region at its N-terminal extremity is essential for virion
export and that the remaining part, dispensable for viral secretion, is
also dispensable for infectivity.
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Role of the Pre-S2 Domain of the Large Envelope
Protein in Hepatitis B Virus Assembly and Infectivity
*
Corresponding author. Mailing address: Unité de
Recherches Hépatologiques, INSERM U 49, Hôpital de
Pontchaillou, 35033 Rennes Cedex, France. Phone: (33) 2 99 54 37 37. Fax: (33) 2 99 54 01 37. E-mail:
Jacques.Leseyec{at}rennes.inserm.fr.
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