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Journal of Virology, April 1999, p. 3351-3358, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Mutations in the Carboxyl-Terminal Domain of the Small Hepatitis B Virus Envelope Protein Impair the Assembly of Hepatitis Delta Virus Particles

Sarah Jenna and Camille Sureau*

Laboratoire de Virologie, Institut de Biologie, 34060 Montpellier, France

Received 16 October 1998/Accepted 8 January 1999

The carboxyl-terminal domain of the small (S) envelope protein of hepatitis B virus was subjected to mutagenesis to identify sequences important for the envelopment of the nucleocapsid during morphogenesis of hepatitis delta virus (HDV) virions. The mutations consisted of carboxyl-terminal truncations of 4 to 64 amino acid residues and small combined deletions and insertions spanning the entire hydrophobic domain between residues 163 and 224. Truncation of as few as 14 residues partially inhibited glycosylation and secretion of S and prevented assembly or stability of HDV virions. Short internal combined deletions and insertions were tolerated for secretion of subviral particles with the exceptions of those affecting residues 164 to 173 and 219 to 223. However, mutants competent for subviral particle secretion had a reduced capacity for HDV assembly compared to that of the wild type. One exception was a mutant carrying a deletion of residues 214 to 218, which exhibited a twofold increase in HDV assembly (or stability), whereas deletions of residues 179 to 183, 194 to 198, and 199 to 203 were the most inhibitory. Substitutions of single amino acids between residues 194 and 198 demonstrated that HDV assembly deficiency could be assigned to the replacement of the tryptophan residue at position 196. We concluded that assembly of stable HDV particles requires a specific function of the carboxyl terminus of S which is mediated at least in part by Trp-196.

* Corresponding author. Mailing address: Laboratoire de Virologie, Institut de Biologie, 2 Blvd. Henri IV, 34060 Montpellier, France. Phone: (33) 4 67 60 27 10. Fax: (33) 4 67 54 23 78. E-mail: csureau{at}sc.univ-montpl.fr.

Journal of Virology, April 1999, p. 3351-3358, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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