在营养限制时,mTORC1-CAD轴的疫苗生长因子依赖调节
Lara Dsouza1, Anil Pant1, Blake Pope1
1Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, Texas, USA.
Journal of virology
|January 16, 2025
概括
疫苗病毒 (VACV) 通过激活病毒生长因子 (VGF) 和mTORC1信号,即使在营养限制下,也通过激活新型金胺合成来重新编程宿主细胞代谢. 这种病毒重编程对于VACV复制至关重要,并具有治疗潜力.
科学领域:
- 病毒学 病毒学
- 细胞的新陈代谢
- 分子生物学分子生物学
背景情况:
- 病毒重新编程宿主细胞代谢以支持复制.
- 疫苗病毒 (VACV) 代谢重编程的机制尚不清楚.
- 皮里米丁的新合成对细胞平衡和病毒感染至关重要.
研究的目的:
- 调查在VACV感染期间新皮里米丁合成的作用.
- 阐明VACV调节这种途径的分子机制.
- 探索针对这种途径进行抗病毒疗法的潜力.
主要方法:
- 研究了VACV感染细胞中CAD酶活性的酸化.
- 使用信号通路分析,包括mTORC1和S6K1.
- 在营养有限的条件下评估了疫苗生长因子 (VGF) 在CAD激活中的作用.
主要成果:
- VACV感染通过酸化CAD酶在血清1859上激活de novo胺合成.
- 这种激活是由病毒蛋白VGF通过mTORC1-S6K1信号轴介导的.
- 即使在氨酸和氨酸限制下,依赖于VGF的CAD激活也会发生,独立于EGF信号.
- 单独的VGF不会激活CAD,这表明其他病毒因素也参与其中.
结论:
- VACV劫持宿主细胞的新陈代谢,特别是新的pyrimidine合成,用于病毒复制.
- 在这种新陈代谢重编程中,VGF起着至关重要的作用.
- 了解这些机制可以导致新的抗病毒策略和改进的基于VACV的治疗方法.
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