The NP protein of Newcastle disease virus dictates its oncolytic activity by regulating viral mRNA translation efficiency

溶瘤病毒 生物 翻译(生物学) 病毒学 信使核糖核酸 病毒 病毒复制 氨基酸 蛋白质生物合成 分子生物学 基因 生物化学
作者
Tianxing Liao,Yu Chen,Lili Guo,Shanshan Zhu,Tiansong Zhan,Xiaolong Lu,Haixu Xu,Zenglei Hu,Jiao Hu,Min Gu,Xiaowen Liu,Xiaoquan Wang,Shunlin Hu,Xiufan Liu
出处
期刊:PLOS Pathogens [Public Library of Science]
卷期号:20 (2): e1012027-e1012027 被引量:2
标识
DOI:10.1371/journal.ppat.1012027
摘要

Newcastle disease virus (NDV) has been extensively studied as a promising oncolytic virus for killing tumor cells in vitro and in vivo in clinical trials. However, the viral components that regulate the oncolytic activity of NDV remain incompletely understood. In this study, we systematically compared the replication ability of different NDV genotypes in various tumor cells and identified NP protein determines the oncolytic activity of NDV. On the one hand, NDV strains with phenylalanine (F) at the 450th amino acid position of the NP protein (450th-F-NP) exhibit a loss of oncolytic activity. This phenotype is predominantly associated with genotype VII NDVs. In contrast, the NP protein with a leucine amino acid at this site in other genotypes (450th-L-NP) can facilitate the loading of viral mRNA onto ribosomes more effectively than 450th-F-NP. On the other hand, the NP protein from NDV strains that exhibit strong oncogenicity interacts with eIF4A1 within its 366–489 amino acid region, leading to the inhibition of cellular mRNA translation with a complex 5’ UTR structure. Our study provide mechanistic insights into how highly oncolytic NDV strains selectively promote the translation of viral mRNA and will also facilitate the screening of oncolytic strains for oncolytic therapy.
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