2. Academic Validation
  3. The HN protein of Newcastle disease virus induces cell apoptosis through the induction of lysosomal membrane permeabilization

The HN protein of Newcastle disease virus induces cell apoptosis through the induction of lysosomal membrane permeabilization

  • PLoS Pathog. 2024 Feb 14;20(2):e1011981. doi: 10.1371/journal.ppat.1011981.
Yu Chen 1 2 3,  Shanshan Zhu 1,  Tianxing Liao 1,  Chunxuan Wang 1,  Jiajun Han 1,  Zhenyu Yang 1,  Xiaolong Lu 1 2 3,  Zenglei Hu 2 4,  Jiao Hu 1 2 3,  Xiaoquan Wang 1 2 3,  Min Gu 1 2 3,  Ruyi Gao 1 2 3,  Kaituo Liu 2 4,  Xiaowen Liu 1 2 3,  Chan Ding 2 5,  Shunlin Hu 1 2 3,  Xiufan Liu 1 2 3
Affiliations

Affiliations

  • 1 Animal Infectious Disease Laboratory, College of Veterinary Medicine, Yangzhou University; Yangzhou, Jiangsu, China.
  • 2 Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, 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, The Ministry of Education of China, Yangzhou University, Yangzhou, China.
  • 5 Department of Avian Infectious Diseases, Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Shanghai, China.
PMID: 38354122 DOI: 10.1371/journal.ppat.1011981
Abstract

Lysosomes are acidic organelles that mediate the degradation and recycling of cellular waste Materials. Damage to lysosomes can cause lysosomal membrane permeabilization (LMP) and trigger different types of cell death, including Apoptosis. Newcastle disease virus (NDV) can naturally infect most birds. Additionally, it serves as a promising oncolytic virus known for its effective Infection of tumor cells and induction of intensive apoptotic responses. However, the involvement of lysosomes in NDV-induced Apoptosis remains poorly understood. Here, we demonstrate that NDV Infection profoundly triggers LMP, leading to the translocation of Cathepsin B and D and subsequent mitochondria-dependent Apoptosis in various tumor and avian cells. Notably, the released Cathepsin B and D exacerbate NDV-induced LMP by inducing the generation of Reactive Oxygen Species. Additionally, we uncover that the viral Hemagglutinin neuraminidase (HN) protein induces the deglycosylation and degradation of lysosome-associated membrane protein 1 (LAMP1) and LAMP2 dependent on its sialidase activity, which finally contributes to NDV-induced LMP and cellular Apoptosis. Overall, our findings elucidate the role of LMP in NDV-induced cell Apoptosis and provide novel insights into the function of HN during NDV-induced LMP, which provide innovative approaches for the development of NDV-based oncolytic agents.

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