在体内以阿波贝克为媒介的逆转录病毒高突变取决于小鼠菌株
Hyewon Byun1, Gurvani B Singh1, Wendy Kaichun Xu1
1Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, United States of America.
PLoS pathogens
|August 29, 2024
概括
小鼠乳腺瘤病毒 (MMTV) 雷姆蛋白影响瘤发生独立于Apobec3介导的病毒变异. 在C57BL/6小鼠中,Rem丧失加速了瘤的发展,但与BALB/c小鼠不同,前病毒突变不受影响.
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:
- 鼠类Apobec3 (mA3) 反对小鼠乳腺瘤病毒 (MMTV) 复制.
- 编码MMTV的Rem蛋白抑制了在BALB/c小鼠中的Apobec介导的前病毒性突变发生.
- 在不同的小鼠菌株中,Rem在MMTV瘤发生中的作用需要进一步调查.
研究的目的:
- 用C57BL/6 (B6) 小鼠研究MMTV Rem蛋白在瘤发生中的体内作用.
- 为了比较B6小鼠与BALB/c小鼠的MMTV易感性和瘤发展.
- 为了确定Rem-mediated对瘤发生的作用是否与B6小鼠的Apobec-mediated前病毒高基因突变有关.
主要方法:
- 野生型B6和B6μMT小鼠感染MMTV菌株TBLV-WT (野生型Rem) 和TBLV-SD (Rem缺陷) 的感染.
- 对瘤发育,前病毒性突变 (高通量测序) 和Apobec3 (mA3) 和激活诱导的cytidine deaminase (AID) 表达 (ex vivo刺激) 的分析.
- 瘤组织的RNA测序 (RNA-Seq) 来识别差异表达的基因和信号通路.
主要成果:
- 与BALB/c小鼠相比,B6小鼠对MMTV感染和瘤发生的敏感性增加.
- 在B6小鼠中,TBLV-SD中的雷姆缺陷加速了瘤发生,不论AID状态如何.
- 预病毒G-to-A/C-to-T突变不依赖Rem在B6瘤中,但AID和mA3淘汰赛减少了突变.
- 与BALB/c相比,B6囊细胞与AID水平相比显示出更高的mA3.
- RNA-Seq揭示了TBLV-SD瘤中生长因子和细胞因子信号转录的增加.
结论:
- 在B6小鼠中对MMTV瘤发生的rem-mediated影响独立于Apobec-mediated的前病毒高突变.
- B6与BALB/c小鼠的独特反应突显了MMTV病原体的菌株特异性差异.
- 雷姆可以通过直接抑制Apobec介导的突变发生的机制以外的其他机制来影响MMTV瘤发生,这可能涉及生长因子和细胞因子信号传递.
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