Thermostable Newcastle disease virus (NDV) vaccines have been used widely to protect village chickens against Newcastle disease, due to their decreased dependence on cold chain for transport and storage. However, the genetic basis underlying the NDV thermostability is poorly understood. In this study, we generated chimeric viruses by exchanging viral genes between the thermostable TS09-C strain and thermolabile LaSota strain using reverse genetics technology. Evaluations of these chimeric NDVs demonstrated that the thermostability of NDV was dependent on the origin of HN protein. Chimeras bearing the HN protein derived from thermostable virus exhibited a thermostable phenotype, and vice versa. Both hemagglutinin and neuraminidase activities of viruses bearing the TS09-C HN protein were more thermostable than those containing LaSota HN protein. Furthermore, the newly developed thermostable virus rLS-T-HN, encoding the TS09-C HN protein in LaSota backbone, induced significantly higher antibody response than the TS09-C virus, and conferred complete protection against virulent NDV challenge. Taken together, the data suggest that the HN protein of NDV is a crucial determinant of thermostability, and the HN gene from a thermostable NDV could be engineered into a thermolabile NDV vaccine strain for developing novel thermostable NDV vaccine.

中文翻译：

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新城疫病毒热稳定性的分子基础。

由于耐高温纽卡斯尔病病毒（NDV）疫苗对运输和储存的依赖性降低，因此已广泛用于保护乡村鸡免于纽卡斯尔病。但是，对NDV热稳定性的遗传基础了解甚少。在这项研究中，我们通过使用逆向遗传技术在热稳定的TS09-C菌株和不耐热的LaSota菌株之间交换病毒基因来产生嵌合病毒。这些嵌合NDV的评估表明NDV的热稳定性取决于HN蛋白的来源。带有衍生自热稳定病毒的HN蛋白的嵌合体表现出热稳定表型，反之亦然。带有TS09-C HN蛋白的病毒的血凝素和神经氨酸酶活性都比含有LaSota HN蛋白的病毒更稳定。此外，新开发的热稳定病毒rLS-T-HN在LaSota主干中编码TS09-C HN蛋白，诱导的抗体应答高于TS09-C病毒，并赋予了针对有毒NDV攻击的完全保护。两者合计，数据表明NDV的HN蛋白是热稳定性的关键决定因素，并且可以将来自热稳定NDV的HN基因工程化为对热不敏感的NDV疫苗株，以开发新型的热稳定NDV疫苗。