African Swine Fever Virus Ubiquitin-Conjugating Enzyme Interacts With Host Translation Machinery to Regulate the Host Protein Synthesis.
African Swine Fever Virus Ubiquitin-Conjugating Enzyme Interacts With Host Translation Machinery to Regulate the Host Protein Synthesis.
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DOI：
10.3389/fmicb.2020.622907
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发表时间：
2020
影响因子：
5.2
通讯作者：
Alonso C
中科院分区：
文献类型：
--
作者：
Barrado-Gil L;Del Puerto A;Muñoz-Moreno R;Galindo I;Cuesta-Geijo MÁ;Urquiza J;Nistal-Villán E;Maluquer de Motes C;Alonso C
非洲猪瘟病毒（ASFV）是影响猪的最相关的新兴疾病之一，目前已蔓延至三大洲。这种病毒有很大的编码能力，可以部署一个分子库来对抗宿主的功能。在目前的工作中，我们研究了唯一已知的E2病毒结合酶，UBCv 1是由ASFV的I215 L基因编码。UBCv 1表达为早期表达蛋白，在整个感染过程中积累。这种多功能蛋白质结合了几种类型的聚泛素链，其催化结构域是酶活性所需的。高通量质谱分析与肺泡巨噬细胞文库的筛选相结合，用于鉴定和表征新型UBCv 1-宿主相互作用物。分析揭示了与40 S核糖体蛋白RPS 23、帽依赖性翻译机制起始因子eIF 4 E和E3遍在蛋白连接酶Cullin 4 B的相互作用。我们的数据表明，在ASFV感染期间，UBCv 1能够与eIF 4 E结合，独立于帽依赖性复合物。我们的研究结果为病毒UBCv 1在劫持细胞组分中的功能提供了新的见解，这些细胞组分影响mTORC信号通路，宿主翻译机制的调节以及ASFV生命周期期间的细胞蛋白表达。
African Swine Fever virus (ASFV) causes one of the most relevant emerging diseases affecting swine, now extended through three continents. The virus has a large coding capacity to deploy an arsenal of molecules antagonizing the host functions. In the present work, we have studied the only known E2 viral-conjugating enzyme, UBCv1 that is encoded by the I215L gene of ASFV. UBCv1 was expressed as an early expression protein that accumulates throughout the course of infection. This versatile protein, bound several types of polyubiquitin chains and its catalytic domain was required for enzymatic activity. High throughput mass spectrometry analysis in combination with a screening of an alveolar macrophage library was used to identify and characterize novel UBCv1-host interactors. The analysis revealed interaction with the 40S ribosomal protein RPS23, the cap-dependent translation machinery initiation factor eIF4E, and the E3 ubiquitin ligase Cullin 4B. Our data show that during ASFV infection, UBCv1 was able to bind to eIF4E, independent from the cap-dependent complex. Our results provide novel insights into the function of the viral UBCv1 in hijacking cellular components that impact the mTORC signaling pathway, the regulation of the host translation machinery, and the cellular protein expression during the ASFV lifecycle.
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