Fusogenic activity of hepadnavirus peptides corresponding to sequences downstream of the putative cleavage site

Citation
I. Rodriguez-crespo et al., Fusogenic activity of hepadnavirus peptides corresponding to sequences downstream of the putative cleavage site, VIROLOGY, 261(1), 1999, pp. 133-142
Citations number
44
Categorie Soggetti
Microbiology
Journal title
VIROLOGY
ISSN journal
00426822 → ACNP
Volume
261
Issue
1
Year of publication
1999
Pages
133 - 142
Database
ISI
SICI code
0042-6822(19990815)261:1<133:FAOHPC>2.0.ZU;2-V
Abstract
Sequence homology between the amino-terminal region of the S protein of hep atitis B Virus (HBV) and known fusion peptides from retroviruses and paramy xoviruses led us to propose that this region might be equally involved in t he initial infective steps of hepadnaviruses. In fact, we showed that a syn thetic peptide corresponding to the N-terminus region of the S protein of H BV had membrane-interacting properties and was able to induce liposome fusi on adopting an extended (beta-sheet) conformation (Rodiguez-Crespo et al., 1996, 1995). We describe herein studies on the interaction of peptides deri ved from the N-terminal region of the S protein of duck (DHBV: Met-Ser-Gly- Thr-Phe-Gly-Gly-Ile-Leu-Ala-Gly-Leu-Ile-Gly-Leu-Leu) and woodchuck hepatiti s B viruses (WHV: Met-Ser-Pro-Ser-Ser-Leu-Leu-Gly-Leu-Leu-Ala-Gly-Leu-Gln-V al-Val) with liposomes. These peptides were able to induce to a different e xtent aggregation, lipid mixing, and leakage of internal aqueous contents f rom both neutral and negatively charged phospholipid vesicles in a concentr ation-dependent and pH-independent manner. Fluorescence depolarization of 1 ,6-diphenyl-1,3,5-hexatriene-labeled vesicles indicated that both peptides become inserted into the hydrophobic core of the lipid bilayer. Circular di chroism studies indicated that the DHBV peptide adopts an extended conforma tion in the presence of lipids, whereas the WHV peptide displays a high con tent of a-helical conformation. Therefore, these results extend our previou s findings obtained for human hepatitis B virus to other members of the hep adnavirus family and suggest that this region of the S protein is important in the initial steps of the infective cycle. (C) 1999 Academic Press.