Fusogenic Activity of Hepadnavirus Peptides Corresponding to Sequences Downstream of the Putative Cleavage Site

• Published in: Virology (New York, N.Y.) Vol. 261; no. 1; pp. 133 - 142
• Main Authors: Rodríguez-Crespo, Ignacio, Núñez, Elena, Yélamos, Belén, Gómez-Gutiérrez, Julián, Albar, Juan P., Peterson, Darrell L., Gavilanes, Francisco
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.08.1999
• Subjects: Amino Acid Sequence; Animals; Circular Dichroism; Duck hepatitis virus; Hepatitis B Virus, Duck - chemistry; Hepatitis B Virus, Duck - metabolism; Hepatitis B Virus, Woodchuck - chemistry; Hepatitis B Virus, Woodchuck - metabolism; Humans; Lipid Bilayers; Liposomes - metabolism; Membrane Fusion; Microscopy, Electron; Molecular Sequence Data; Peptides - chemical synthesis; Peptides - chemistry; Peptides - metabolism; Phospholipids - metabolism; Temperature; Viral Envelope Proteins - chemistry; Viral Envelope Proteins - genetics; Viral Envelope Proteins - metabolism; Viral Fusion Proteins - chemistry; Viral Fusion Proteins - metabolism
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.1999.9823

Sequence homology between the amino-terminal region of the S protein of hepatitis B Virus (HBV) and known fusion peptides from retroviruses and paramyxoviruses led us to propose that this region might be equally involved in the initial infective steps of hepadnaviruses. In fact, we showed that a synthetic peptide corresponding to the N-terminus region of the S protein of HBV had membrane-interacting properties and was able to induce liposome fusion adopting an extended (β-sheet) conformation (Rodrı́guez-Crespo et al., 1996, 1995). We describe herein studies on the interaction of peptides derived 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 hepatitis B viruses (WHV: Met-Ser-Pro-Ser-Ser-Leu-Leu-Gly-Leu-Leu-Ala-Gly-Leu-Gln-Val-Val) with liposomes. These peptides were able to induce to a different extent aggregation, lipid mixing, and leakage of internal aqueous contents from both neutral and negatively charged phospholipid vesicles in a concentration-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 dichroism studies indicated that the DHBV peptide adopts an extended conformation in the presence of lipids, whereas the WHV peptide displays a high content of α-helical conformation. Therefore, these results extend our previous findings obtained for human hepatitis B virus to other members of the hepadnavirus family and suggest that this region of the S protein is important in the initial steps of the infective cycle.