Interaction domain of glycoproteins gB and gH of Marek's disease virus and identification of an antiviral peptide with dual functions.
Interaction domain of glycoproteins gB and gH of Marek's disease virus and identification of an antiviral peptide with dual functions.
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DOI：
10.1371/journal.pone.0054761
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang M
中科院分区：
文献类型：
--
作者：
Chi XJ;Lu YX;Zhao P;Li CG;Wang XJ;Wang M
我们以前的研究报告疱疹病毒马立克氏病病毒（MDV）的糖蛋白gB和gH都含有11个潜在的七肽重复结构域。这些结构域与α-螺旋富集的疏水区域重叠，包括gH衍生的HR 1（gHH 1）和HR 3（gHH 3）以及gB衍生的HR 1（gBH 1）区域，这些区域显示出有效的抗病毒活性，50%抑制浓度（IC 50）小于12 µM。空斑形成和鸡胚感染试验证实了这些结果。在这项研究中，生化和生物物理分析检测到了这些肽之间潜在的相互作用。发现gHH 1、gHH 3和gBH 1彼此成对地相互作用。在摩尔比为1：3时，gHH 3与gBH 1形成的复合物相互作用最稳定，gHH 1与gBH 1之间的结合相对较弱，3种HR肽之间未观察到相互作用。这些结果表明，gHH 3和gBH 1可能是gB和gH之间相互作用的关键贡献者。此外，与来自I类包膜病毒的肽相比，来自疱疹病毒糖蛋白的每个HR肽不能有效地抑制病毒感染。在本报告中，在非相互作用位点（即，溶剂可及位点）与野生型HR肽相比不显著影响抗病毒活性，而来自gH衍生的gHH 1和gB衍生的gBH 1的串联肽（即，gBH 1-接头-gHH 1）产生有效的抗病毒作用，这与单个肽不同。对禁止进入的拟议解释进行了讨论。我们的研究结果支持了这样的假设，即糖蛋白gH和gB之间的相互作用域是疱疹病毒感染抑制剂设计的关键目标。
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 (IC50) 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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