Carpio Kassandra L, Barrett Alan D T
Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Vaccines (Basel). 2021 Jun 9;9(6):622. doi: 10.3390/vaccines9060622.
The Flavivirus genus contains many important human pathogens, including dengue, Japanese encephalitis (JE), tick-borne encephalitis (TBE), West Nile (WN), yellow fever (YF) and Zika (ZIK) viruses. While there are effective vaccines for a few flavivirus diseases (JE, TBE and YF), the majority do not have vaccines, including WN and ZIK. The flavivirus nonstructural 1 (NS1) protein has an unusual structure-function because it is glycosylated and forms different structures to facilitate different roles intracellularly and extracellularly, including roles in the replication complex, assisting in virus assembly, and complement antagonism. It also plays a role in protective immunity through antibody-mediated cellular cytotoxicity, and anti-NS1 antibodies elicit passive protection in animal models against a virus challenge. Historically, NS1 has been used as a diagnostic marker for the flavivirus infection due to its complement fixing properties and specificity. Its role in disease pathogenesis, and the strong humoral immune response resulting from infection, makes NS1 an excellent target for inclusion in candidate flavivirus vaccines.
黄病毒属包含许多重要的人类病原体，包括登革热病毒、日本脑炎病毒（JE）、蜱传脑炎病毒（TBE）、西尼罗河病毒（WN）、黄热病病毒（YF）和寨卡病毒（ZIK）。虽然有针对几种黄病毒疾病（JE、TBE和YF）的有效疫苗，但大多数黄病毒疾病（包括WN和ZIK）没有疫苗。黄病毒非结构蛋白1（NS1）具有不同寻常的结构功能，因为它是糖基化的，并且会形成不同的结构以在细胞内和细胞外发挥不同作用，包括在复制复合体中的作用、协助病毒组装以及补体拮抗作用。它还通过抗体介导的细胞毒性在保护性免疫中发挥作用，并且抗NS1抗体在动物模型中可引发针对病毒攻击的被动保护作用。从历史上看，由于NS1的补体固定特性和特异性，它一直被用作黄病毒感染的诊断标志物。其在疾病发病机制中的作用以及感染所引发的强烈体液免疫反应，使得NS1成为候选黄病毒疫苗中的一个极佳靶点。
