A plant nonenveloped double-stranded RNA virus activates and co-opts BNIP3-mediated mitophagy to promote persistent infection in its insect vector
A plant nonenveloped double-stranded RNA virus activates and co-opts BNIP3-mediated mitophagy to promote persistent infection in its insect vector
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DOI：
10.1080/15548627.2022.2091904
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发表时间：
2022-06
期刊：
影响因子：
13.3
通讯作者：
Qifu Liang;Jiajia Wan;Huan Liu;Dongsheng Jia;Qian Chen;Aiming Wang;T. Wei
中科院分区：
文献类型：
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作者：
Qifu Liang;Jiajia Wan;Huan Liu;Dongsheng Jia;Qian Chen;Aiming Wang;T. Wei
摘要有丝分裂选择性地消除受损的线粒体是线粒体质量控制的重要机制。最近，一些动物病毒感染的宿主细胞被证明可以诱导有丝分裂。在这里，我们报道了南方水稻黑条矮缩病毒(SRBSDV)，一种植物无包膜双链RNA病毒，也可以在其飞虱载体上触发有丝分裂，以防止线粒体依赖性的细胞凋亡，促进病毒的持续繁殖。我们发现，SRBSDV的非结构蛋白P7-1构建的纤维结构通过与线粒体吞噬受体BNIP3(BCL2相互作用蛋白3)的相互作用直接靶向线粒体，这些线粒体被隔离在自噬体内形成有丝吞噬小体。此外，SRBSDV感染或单独表达P7-1可促进BNIP3在线粒体上的二聚化，并通过P7-1-ATG8相互作用诱导自噬。此外，SRBSDV感染可通过AMPKα-BNIP3相互作用刺激AMPK的磷酸化，导致BNIP3的磷酸化。总之，P7-1通过促进线粒体上磷酸化的BNIP3二聚体的形成来诱导BNIP3介导的有丝分裂吞噬。沉默ATG8、BNIP3或AMPKα显著减少病毒诱导的有丝分裂和病毒在昆虫载体中的繁殖。这些数据表明，在稻飞虱中，SRBSDV诱导的有丝噬菌体被修改以适应病毒粒子并促进病毒的持续传播。总之，我们的结果表明，病毒蛋白通过连接自噬小体和线粒体，在诱导BNIP3介导的有丝分裂方面发挥了以前未被认识的作用，并揭示了病毒诱导的有丝分裂在维持昆虫载体中持续病毒感染方面的功能重要性。缩写：AMPK：AMP激活的蛋白激酶；ATG：自噬相关；BNIP3：BCL2相互作用蛋白3；CASP3：caspase3；dsRNA：双链rna；ER：内质网；FITC：异硫氰酸荧光素；FKBP8：FBP-Kprolyl异构酶8；Func1：包含FUN14结构域；GFP：绿色荧光蛋白；GST：谷胱甘肽-S-酶；PAP：首先进入病株；PHOS-Tag：磷酸结合标签；PINK1：PTEN诱导的蛋白1；Sf9：果蝇夜蛾；SQSTM1：隔离小体1；SRBSDV：南方水稻黑条矮缩病毒；STK11/LKB1：丝氨酸/苏氨酸激酶11；TOMM20：线粒体外膜转位酶20；RBSDV：水稻黑条矮缩病毒；Tunel：末端脱氧核苷酸dUTP缺口末端标记；ULK1：UNC-51样自噬激活蛋白1；VDAC1：电压依赖性阴离子通道1。
ABSTRACT Mitophagy that selectively eliminates damaged mitochondria is an essential mitochondrial quality control mechanism. Recently, mitophagy has been shown to be induced in host cells infected by a few animal viruses. Here, we report that southern rice black-streaked dwarf virus (SRBSDV), a plant nonenveloped double-stranded RNA virus, can also trigger mitophagy in its planthopper vector to prevent mitochondria-dependent apoptosis and promote persistent viral propagation. We find that the fibrillar structures constructed by the nonstructural protein P7-1 of SRBSDV directly target mitochondria via interaction with the mitophagy receptor BNIP3 (BCL2 interacting protein 3), and these mitochondria are then sequestered within autophagosomes to form mitophagosomes. Moreover, SRBSDV infection or P7-1 expression alone can promote BNIP3 dimerization on the mitochondria, and induce autophagy via the P7-1-ATG8 interaction. Furthermore, SRBSDV infection stimulates the phosphorylation of AMP-activated protein kinase (AMPK), resulting in BNIP3 phosphorylation via the AMPKα-BNIP3 interaction. Together, P7-1 induces BNIP3-mediated mitophagy by promoting the formation of phosphorylated BNIP3 dimers on the mitochondria. Silencing of ATG8, BNIP3, or AMPKα significantly reduces virus-induced mitophagy and viral propagation in insect vectors. These data suggest that in planthopper, SRBSDV-induced mitophagosomes are modified to accommodate virions and facilitate persistent viral propagation. In summary, our results demonstrate a previously unappreciated role of a viral protein in the induction of BNIP3-mediated mitophagy by bridging autophagosomes and mitochondria and reveal the functional importance of virus-induced mitophagy in maintaining persistent viral infection in insect vectors.Abbreviations: AMPK: AMP-activated protein kinase; ATG: autophagy related; BNIP3: BCL2 interacting protein 3; CASP3: caspase 3; dsRNA: double strand RNA; ER: endoplasmic reticulum; FITC: fluorescein isothiocyanate; FKBP8: FKBP prolyl isomerase 8; FUNDC1: FUN14 domain containing 1; GFP: green fluorescent protein; GST: glutathione S-transferase; padp: post-first access to diseased plants; Phos-tag: Phosphate-binding tag; PINK1: PTEN induced kinase 1; Sf9: Spodoptera frugiperda; SQSTM1: sequestosome 1; SRBSDV: southern rice black-streaked dwarf virus; STK11/LKB1: serine/threonine kinase 11; TOMM20: translocase of outer mitochondrial membrane 20; RBSDV: rice black-streaked dwarf virus; TUNEL: terminal deoxynucleotidyl dUTP nick end labeling; ULK1: unc-51 like autophagy activating kinase 1; VDAC1: voltage dependent anion channel 1.