在vivo中,阿波贝克介导的逆转录病毒高基突变依赖于小鼠菌株
bioRxiv : the preprint server for biology
|November 14, 2023
概括
小鼠乳腺瘤病毒 (MMTV) 的Rem蛋白是小鼠乳腺瘤病毒.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
背景情况:
- 小鼠乳腺瘤病毒 (MMTV) 复制被小鼠Apobec3 (mA3) 抑制.
- 在病毒复制过程中,MMTV Rem蛋白抑制了Apobec介导的突变发生.
- 雷姆在MMTV瘤发生中的作用需要进一步调查.
研究的目的:
- 研究MMTV Rem蛋白在病毒复制和瘤发生中的体内作用.
- 为了比较Rem对MMTV感染和瘤发育在不同小鼠菌株的影响.
- 阐明REM介导作用对MMTV诱导瘤的潜在机制.
主要方法:
- 在C57BL/6 (B6) 和BALB/c小鼠中感染野生型 (TBLV-WT) 和Rem缺陷型 (TBLV-SD) MMTV菌株.
- 使用高通量测序分析病毒复制,瘤发育和前病毒突变.
- 在脊髓细胞中评估Apobec3 (mA3) 和激活诱导的cytidine deaminase (AID) 水平.
- 瘤组织的RNA测序 (RNA-Seq) 来识别差异表达的基因.
主要成果:
- 雷姆缺乏在B6小鼠中加速MMTV诱导的瘤发生,独立于Apobec介导的高突变.
- 与BALB/c小鼠相比,B6小鼠对MMTV感染和瘤发展的敏感性更高.
- 与BALB/c小鼠相比,B6小鼠的脊髓细胞与AID相比显示出较高的mA3水平.
- 与TBLV-WT瘤相比,TBLV-SD诱导的瘤显示了与生长因子和细胞因子信号传递相关的转录的增加.
结论:
- 在B6小鼠中MMTV Rem蛋白在瘤发生中的作用独立于Apobec介导的前病毒性突变.
- 雷姆除了抑制阿波贝克活性之外,可能还具有其他功能,可能涉及生长因子和细胞因子信号传递.
- 主体遗传学的差异 (B6与BALB/c) 影响MMTV易感性和瘤发生.
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