细胞凋亡
细胞生物学
溶瘤病毒
生物
灯1
程序性细胞死亡
组织蛋白酶B
组织蛋白酶D
溶酶体
病毒
组织蛋白酶
病毒学
自噬
生物化学
酶
作者
Yu Chen,Shanshan Zhu,Tianxing Liao,Chunxuan Wang,Jianxun Han,Zhenyu Yang,Xiaolong Lü,Zenglei Hu,Jiao Hu,Xiaoquan Wang,Min Gu,Ruyi Gao,Kaituo Liu,Xiaowen Liu,Chan Ding,Shunlin Hu,Xiufan Liu
出处
期刊:PLOS Pathogens
[Public Library of Science]
日期:2024-02-14
卷期号:20 (2): e1011981-e1011981
标识
DOI:10.1371/journal.ppat.1011981
摘要
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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