2. Academic Validation
  3. The NP protein of Newcastle disease virus dictates its oncolytic activity by regulating viral mRNA translation efficiency

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

  • PLoS Pathog. 2024 Feb 20;20(2):e1012027. doi: 10.1371/journal.ppat.1012027.
Tianxing Liao 1,  Yu Chen 1,  Lili Guo 1,  Shanshan Zhu 1,  Tiansong Zhan 1,  Xiaolong Lu 1,  Haixu Xu 1,  Zenglei Hu 1 2 3 4,  Jiao Hu 1 2,  Min Gu 1 3,  Xiaowen Liu 1 2,  Xiaoquan Wang 1,  Shunlin Hu 1 2 3,  Xiufan Liu 1 2 3 4
Affiliations

Affiliations

  • 1 Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University, Yangzhou, China.
  • 2 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infections Diseases and Zoonoses, Yangzhou University, Yangzhou, China.
  • 3 Jiangsu Key Laboratory of Zoonosis, Yangzhou University, Yangzhou, China.
  • 4 Joint International Research Laboratory of Agriculture and Agri-Product Safety, Ministry of Education of China, Yangzhou University, Yangzhou, China.
PMID: 38377149 DOI: 10.1371/journal.ppat.1012027
Abstract

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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