Herpesvirus lytic infection-induced mitophagy via viral interferon regulatory factor 1.
Herpesvirus lytic infection-induced mitophagy via viral interferon regulatory factor 1.
复制标题
疱疹病毒裂解感染通过病毒干扰素调节因子 1 诱导线粒体自噬。
DOI：
10.1080/27694127.2023.2281135
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Choi,YoungBong
中科院分区：
文献类型：
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作者：
Vo,MaiTram;Choi,YoungBong
病毒通过线粒体自噬控制线粒体对线粒体介导的先天免疫应答具有抑制作用。我们以前发现，人类疱疹病毒8型（HHV-8）可以通过其裂解基因产物vIRF-1（病毒干扰素调节因子1）激活线粒体自噬。从机制上讲，我们以前证明了vIRF-1与线粒体吞噬蛋白BNIP 3L（BCL 2相互作用蛋白3样）和TUFM（Tu翻译延伸因子，线粒体）相互作用。尽管有这些重要的发现，然而，vIRF-1激活的线粒体自噬的确切分子机制，特别是自噬机制的核心成分，仍然有待充分阐明。我们最近报道，vIRF-1优先和直接结合GABARAPL 1（GABA A型受体相关蛋白样1）在一个非经典的方式，这种相互作用是必不可少的病毒生产复制。此外，我们发现BNIP 3L是促进vIRF-1寡聚化和相关的线粒体自噬激活的关键因子，包括GABARAPL 1与vIRF-1的相互作用和TUFM二聚化。缩写：ATG 8，自噬相关基因8; BNIP 3L，BCL 2相互作用蛋白3样; HHV-8，人类疱疹病毒8; GABARAP，GABA A型受体相关蛋白; GABARAPL 1，GABARAP样1; LC 3，微管相关蛋白1轻链3; LIR，LC 3相互作用区; Nix，NIP 3样蛋白X; TUFM，Tu翻译延伸因子，线粒体; vIRF-1，病毒干扰素调节因子1; UIM，泛素相互作用基序; VIR，vIRF-1相互作用区。
Viral control of mitochondria via mitophagy has a dampening effect on mitochondrion-mediated innate immune responses. We previously found that human herpesvirus 8 (HHV-8) could activate mitophagy via its lytic gene product vIRF-1 (viral interferon regulatory factor 1). Mechanistically, we previously demonstrated that vIRF-1 interacts with the mitophagic proteins BNIP3L (BCL2 interacting protein 3 like) and TUFM (Tu translation elongation factor, mitochondrial). Despite these significant findings, however, the precise molecular mechanisms underlying vIRF-1-activated mitophagy, particularly with core components of the autophagy machinery, remained to be fully elucidated. We recently reported that vIRF-1 binds preferentially and directly to GABARAPL1 (GABA type A receptor associated protein like 1) in a noncanonical manner, and this interaction is essential for virus-productive replication. Furthermore, we found that BNIP3L is a crucial factor that promotes vIRF-1 oligomerization and associated mitophagy activation, including GABARAPL1 interaction with vIRF-1 and TUFM dimerization. Together, our findings deepen our understanding of lytic infection-induced mitophagy and provide the key protein-protein interactions involved in vIRF-1-mediated mitophagy.Abbreviations:ATG8, autophagy-related gene 8; BNIP3L, BCL2 interacting protein 3 like; HHV-8, human herpesvirus 8; GABARAP, GABA type A receptor associated protein; GABARAPL1, GABARAP-like 1; LC3, microtubule-associated protein 1 light chain 3; LIR, LC3-interacting region; Nix, NIP3-like protein X; TUFM, Tu translation elongation factor, mitochondria; vIRF-1, viral interferon regulatory factor 1; UIM, ubiquitin-interacting motif; VIR, vIRF-1-interacting region.