过氧化物酶体穿梭蛋白PEX5调控新城疫病毒诱导的细胞凋亡

doi:10.1016/j.jia.2024.08.016

摘要/Abstract

摘要：

新城疫病毒（Newcastle disease virus，NDV）是一种具有高致病性和高度传染性的病毒，同时也是一种能够在肿瘤细胞中选择性复制的溶瘤病毒。NDV在禽类和肿瘤细胞中具有高复制效率，能够引发多种细胞死亡方式，包括铁死亡、坏死、细胞凋亡和自噬性细胞死亡。其中，细胞凋亡作为一种重要的程序性细胞死亡方式，其在NDV感染过程中的研究最为深入。细胞器在调控和执行细胞凋亡过程中发挥着至关重要的作用。然而，关于过氧化物酶体这种重要的细胞器在病毒诱导的细胞凋亡中的作用尚未完全明确。本研究的目的是探讨NDV感染过程中，过氧化物酶体在细胞凋亡调控中的具体作用机制，特别是过氧化物酶体生物合成相关基因在NDV感染后的表达变化，以及这种变化对细胞凋亡的影响。研究结果表明，NDV感染显著下调了细胞内多个过氧化物酶体生物合成相关基因的mRNA水平，其中PEX5基因的下调最为显著，且其蛋白水平也明显降低。在PEX5敲除细胞系中，NDV诱导的细胞凋亡显著增加，而在稳定表达PEX5的细胞系中，NDV诱导的细胞凋亡显著减少。这表明PEX5在调控NDV诱导的细胞凋亡中发挥了重要的保护作用。进一步的研究发现，PEX5通过调节抗凋亡蛋白Bcl-2的表达来抑制NDV诱导的细胞凋亡。本研究首次揭示了NDV通过下调过氧化物酶体穿梭蛋白PEX5来调节NDV诱导的细胞凋亡。这一发现揭示了过氧化物酶体在调控病毒诱导的细胞凋亡过程中的潜在作用，为进一步理解NDV的致病机制和细胞凋亡的调控机制提供了新的视角。

Abstract:

Newcastle disease virus (NDV) is a highly lethal and contagious viral pathogen; it is also a potent oncolytic virus that selectively replicates in tumor cells. NDV demonstrates high replication efficiency in avian and tumor cells, causing various types of cell death, including ferroptosis, necrosis, apoptosis and autophagic cell death, with apoptosis being the most thoroughly studied. Organelles play critical and distinctive roles in the regulation and execution of apoptosis. However, the involvement of peroxisomes, an important organelle that regulates redox balance and lipid biosynthesis, in virus-induced apoptosis remains unclear. Our findings reveal that NDV infection promotes the downregulation of several peroxisome biogenesis factors (PEXs) at the mRNA level. Peroxisomal biogenesis factor 5 (PEX5), a critical peroxisomal shuttle protein, was identified to be significantly downregulated at both the mRNA and protein levels. Further, gain- and loss-of-function experiments demonstrated the negative regulation of NDV-induced apoptosis by PEX5. In addition, PEX5 inhibits NDV-induced apoptosis by regulating the anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) expression. These findings reveal a novel mechanism by which NDV-induced apoptosis is modulated through the downregulation of PEXs, particularly PEX5, shedding light on the potential role of peroxisome in apoptosis regulation in response to virus infection.

Key words: NDV , peroxisome , , PEX5 , , Bcl-2 , , apoptosis

. 过氧化物酶体穿梭蛋白PEX5调控新城疫病毒诱导的细胞凋亡[J]. Journal of Integrative Agriculture, DOI: 10.1016/j.jia.2024.08.016.

Hui Jiang, Yanfeng Liu, Ying Liao, Xusheng Qiu, Lei Tan, Cuiping Song, Chan Ding, Yingjie Sun. PEX5-mediated modulation of apoptotic pathways in response to Newcastle disease virus infection[J]. Journal of Integrative Agriculture, DOI: 10.1016/j.jia.2024.08.016.

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