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Interaction Domain of Glycoproteins gB and gH of Marek's Disease Virus and Identification of an Antiviral Peptide with Dual Functions

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 (gB...

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Autores principales: Chi, Xiao-Jing, Lu, Yi-Xin, Zhao, Peng, Li, Chuan-Gen, Wang, Xiao-Jia, Wang, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566115/
https://www.ncbi.nlm.nih.gov/pubmed/23405092
http://dx.doi.org/10.1371/journal.pone.0054761
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author Chi, Xiao-Jing
Lu, Yi-Xin
Zhao, Peng
Li, Chuan-Gen
Wang, Xiao-Jia
Wang, Ming
author_facet Chi, Xiao-Jing
Lu, Yi-Xin
Zhao, Peng
Li, Chuan-Gen
Wang, Xiao-Jia
Wang, Ming
author_sort Chi, Xiao-Jing
collection PubMed
description 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.
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spelling pubmed-35661152013-02-12 Interaction Domain of Glycoproteins gB and gH of Marek's Disease Virus and Identification of an Antiviral Peptide with Dual Functions Chi, Xiao-Jing Lu, Yi-Xin Zhao, Peng Li, Chuan-Gen Wang, Xiao-Jia Wang, Ming PLoS One Research Article 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. Public Library of Science 2013-02-06 /pmc/articles/PMC3566115/ /pubmed/23405092 http://dx.doi.org/10.1371/journal.pone.0054761 Text en © 2013 Chi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Chi, Xiao-Jing
Lu, Yi-Xin
Zhao, Peng
Li, Chuan-Gen
Wang, Xiao-Jia
Wang, Ming
Interaction Domain of Glycoproteins gB and gH of Marek's Disease Virus and Identification of an Antiviral Peptide with Dual Functions
title Interaction Domain of Glycoproteins gB and gH of Marek's Disease Virus and Identification of an Antiviral Peptide with Dual Functions
title_full Interaction Domain of Glycoproteins gB and gH of Marek's Disease Virus and Identification of an Antiviral Peptide with Dual Functions
title_fullStr Interaction Domain of Glycoproteins gB and gH of Marek's Disease Virus and Identification of an Antiviral Peptide with Dual Functions
title_full_unstemmed Interaction Domain of Glycoproteins gB and gH of Marek's Disease Virus and Identification of an Antiviral Peptide with Dual Functions
title_short Interaction Domain of Glycoproteins gB and gH of Marek's Disease Virus and Identification of an Antiviral Peptide with Dual Functions
title_sort interaction domain of glycoproteins gb and gh of marek's disease virus and identification of an antiviral peptide with dual functions
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566115/
https://www.ncbi.nlm.nih.gov/pubmed/23405092
http://dx.doi.org/10.1371/journal.pone.0054761
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