多原体分析确定了宿主细胞通路被传播的脑炎病毒感染扰乱
Liyan Sui1, Wenfang Wang1,2, Xuerui Guo3
1Department of Infectious Diseases and Center of Infectious Diseases and Pathogen Biology, Key Laboratory of Organ Regeneration and Transplantation of the Ministry of Education, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital of Jilin University, Changchun, China.
Nature communications
|November 30, 2024
概括
感染性脑炎病毒 (TBEV) 破坏细胞过程,如DNA修复和自. 针对这些途径提供了针对TBEV和相关的病毒的潜在抗病毒策略.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 传染性脑炎病毒 (TBEV) 在欧洲和亚洲引起严重的神经疾病.
- 新出现的突变,疫苗的突破,以及缺乏对相关的黄病毒的治疗方法,需要了解TBEV的病原性.
研究的目的:
- 为了阐明TBEV感染期间细胞蛋白质组,蛋白质组和乙蛋白质组的变化.
- 为了确定参与TBEV病变的宿主途径和病毒机制.
- 探索潜在的抗病毒干预目标.
主要方法:
- 对TBEV感染细胞进行蛋白质组,蛋白质组和蛋白质组分析.
- 研究病毒蛋白与宿主因子 (NS5,prM与SIRT1,KAP1,Ku70,AKT1,VPS11) 的相互作用.
- 对DDR和激酶抑制剂的抗病毒活性进行评估.
主要成果:
- TBEV感染显著影响天生的免疫力,核糖体生物发生,自和DNA损伤反应 (DDR).
- 通过SIRT1相互作用抑制KAP1和Ku70脱乙烯化,TBEV NS5蛋白抑制DNA修复.
- TBEV prM 蛋白通过 AKT1 诱导自,但通过结合 VPS11 来阻碍自解酶体的形成.
结论:
- TBEV操纵宿主细胞通路,包括自和DDR,用于其复制.
- 鉴定出失调的通路和激酶是抗病毒疗法的潜在目标.
- 这些发现为开发有效治疗TBEV和其他传播的病毒提供了洞察力.
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