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首页> 外文期刊>Veterinary Immunology and Immunopathology >Virus, strain, and epitope specificities of neutralizing bovine monoclonal antibodies to bovine herpesvirus 1 glycoproteins gB, gC, and gD, with sequence and molecular model analysis
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Virus, strain, and epitope specificities of neutralizing bovine monoclonal antibodies to bovine herpesvirus 1 glycoproteins gB, gC, and gD, with sequence and molecular model analysis

机译：用序列和分子模型分析中和牛疱疹病毒1糖蛋白gB，gC和gD的牛单克隆抗体的病毒，毒株和表位特异性

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摘要

Three bovine monoclonal antibodies (BomAb) raised to bovine herpesvirus (BoHV) 1.1 and specific for the viral glycoproteins gB, gC, and gD were tested for reactivity to two isolates of BoHV-1.1, one of BoHV-1.2, and two of BoHV-5 in virus neutralization and indirect fluorescent antibody assays. They were also tested with other herpesviruses infecting cattle and other mammalian alphaherpesviruses, and found negative or of negligible reactivity. Their BoHV-1.1 epitope specificity was examined using competitive ELISA with peroxidase-labeled murine monoclonal antibodies (MumAb) that had been previously characterized. To explain the incongruities observed, the amino acid sequences of the epitopes and adjacent regions of BoHV-1.1, 1.2, and 5 were compared, and molecular modeling was performed using human herpesvirus 1 glycoprotein crystals as templates. The anti-gB BomAb reacted strongly with BoHV-1.1 and BoHV-1.2, and poorly or not at all with BoHV-5. It competed with a MumAb specific for a BoHV-1.1 gB epitope previously shown to only partially cross-react between BoHV-1 and BoHV-5. BoHV-5 gB has nearly identical sequence with BoHV-1.1 in the epitope region, but modeling suggested the lack of cross-reactivity of the MumAb was due to masking of the epitope in BoHV-5 by an adjacent region, which has significant sequence differences between BoHV-1.1 and BoHV-5. The BomAb reactivity could also be explained by masking, or by reactivity with the adjacent region. The anti-gC BomAb reacted strongly with one isolate of BoHV-1.1 and BoHV-1.2, less well with a heterologous isolate of BoHV-1.1, and poorly or not at all with BoHV-5. It did not compete with any of the anti-gC MumAb tested, but a target domain was suggested by BoHV-1.1, 1.2, and 5 sequence divergence. The anti-gD BomAb reacted strongly with all BoHV-1.1, 1.2, and 5 isolates tested. However, it competed with two MumAb previously shown to not cross-react between BoHV-1.1 and BoHV-5. Sequence analysis and modeling suggested the cross-reactivity of the anti-gD BomAb was due to it reacting with an epitope-adjacent region or regions conserved between BoHV-1.1 and BoHV-5, but not with other alphaherpesviruses. The results suggest the usefulness of combining in vitro biological data with sequence or structure modeling data to investigate important epitopes involved in immunity to infectious agents. Published by Elsevier B.V.
机译：测试了三种针对牛疱疹病毒（BoHV）1.1且对病毒糖蛋白gB，gC和gD具有特异性的牛单克隆抗体（BomAb）与BoHV-1.1的两种分离物，BoHV-1.2的一种和BoHV-1.2的两种的反应性5在病毒中和和间接荧光抗体检测中。他们还用其他感染牛的疱疹病毒和其他哺乳动物的α疱疹病毒进行了测试，发现它们的反应性为阴性或微不足道。使用竞争性ELISA和过氧化物酶标记的鼠类单克隆抗体（MumAb）检验了它们的BoHV-1.1表位特异性，该抗体先前已进行了表征。为了解释观察到的不一致，比较了BoHV-1.1、1.2和5的抗原决定簇和邻近区域的氨基酸序列，并使用人疱疹病毒1糖蛋白晶体作为模板进行了分子建模。抗gB BomAb与BoHV-1.1和BoHV-1.2反应强烈，而与BoHV-5反应差或根本不反应。它与特异性针对BoHV-1.1 gB表位的MumAb竞争，以前显示仅在BoHV-1和BoHV-5之间发生部分交叉反应。 BoHV-5 gB在表位区域具有与BoHV-1.1几乎相同的序列，但是建模表明MumAb缺乏交叉反应性是由于BoHV-5中的表位被相邻区域掩盖了，这具有显着的序列差异在BoHV-1.1和BoHV-5之间。 BomAb反应性也可以通过掩盖或与相邻区域的反应来解释。抗gC BomAb与BoHV-1.1和BoHV-1.2的一种分离物强烈反应，与BoHV-1.1的异源分离物反应不好，而与BoHV-5则反应差或根本不反应。它没有与任何测试的抗gC MumAb竞争，但是BoHV-1.1、1.2和5序列差异提示了一个目标域。抗gD BomAb与所有测试的BoHV-1.1、1.2和5分离株反应强烈。但是，它与先前证明在BoHV-1.1和BoHV-5之间不会发生交叉反应的两种MumAb竞争。序列分析和建模表明，抗gD BomAb的交叉反应性是由于它与表位相邻区域或BoHV-1.1和BoHV-5之间的保守区域反应，而不与其他α疱疹病毒反应。结果表明将体外生物学数据与序列或结构建模数据相结合以研究涉及对传染原的免疫力的重要表位的有用性。由Elsevier B.V.发布

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