Interaction domain of glycoproteins gB and gH of Marek's disease virus and identification of an antiviral peptide with dual functions.

Abstract

Our previous study reported that both glycoproteins gB and gH of the herpesvirus Marek's disease virus (MDV) contain eleven potential heptad repeat domains. These domains overlap with α-helix-enriched hydrophobic regions, including the gH-derived HR1 (gHH1) and HR3 (gHH3) and gB-derived HR1 (gBH1) regions, which demonstrate effective antiviral activity, with 50% inhibitory concentrations (IC(50)) of less than 12 µM. Plaque formation and chicken embryo infection assays confirmed these results. In this study, biochemical and biophysical analyses detected potential interactions between these peptides. gHH1, gHH3, and gBH1 were found to interact with each other in pairs. The complex formed by gHH3 and gBH1 showed the most stable interaction at a molar ratio of 1:3, the binding between gHH1 and gBH1 was relatively weak, and no interaction was observed between the three HR peptides. These results indicate that gHH3 and gBH1 are likely the key contributors to the interaction between gB and gH. Furthermore, each HR peptide from herpesvirus glycoproteins did not effectively inhibit virus infection compared with peptides from a class I enveloped virus. In this report, the HR mimic peptide modified with a double glutamic acid (EE) or a double lysine (KK) at the non-interactive sites (i.e., solvent-accessible sites) did not noticeably affect the antiviral activity compared with the wild-type HR peptide, whereas tandem peptides from gH-derived gHH1 and gB-derived gBH1 (i.e., gBH1-Linker-gHH1) produced efficient antiviral effects, unlike the individual peptides. The proposed interpretation of inhibition of entry has been addressed. Our results support the hypothesis that the interaction domain between glycoproteins gH and gB is a critical target in the design of inhibitors of herpesvirus infection.

• Authors: Xiao-Jing Chi, Yi-Xin Lu, Peng Zhao, Chuan-Gen Li, Xiao-Jia Wang, Ming Wang
• Journal: PloS one (PLoS One) Vol. 8 Issue 2 Pg. e54761 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23405092 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Viral
• Antiviral Agents
• Peptides
• Viral Envelope Proteins
• glycoprotein B, Marek's disease virus
• glycoprotein H, Marek's disease virus

Topics

• Amino Acid Sequence
• Animals
• Antigens, Viral (metabolism)
• Antiviral Agents (chemistry, pharmacology)
• Chick Embryo
• Fibroblasts (virology)
• Herpesvirus 2, Gallid (metabolism)
• Molecular Sequence Data
• Peptides (chemistry, pharmacology)
• Protein Binding
• Protein Interaction Domains and Motifs
• Protein Structure, Secondary
• Protein Structure, Tertiary
• Viral Envelope Proteins (metabolism)