内在的p53激活在延迟建立期间限制了马疹病毒驱动的生殖中心B细胞扩张
Shana M Owens1, Jeffrey M Sifford1, Gang Li1
1Dept. of Microbiology and Immunology and Center for Microbial Pathogenesis and Host Inflammatory Responses, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Nature communications
|January 22, 2025
概括
瘤抑制剂p53通过限制受感染B细胞的增殖来控制马疹病毒 (GHV) 感染. 损失p53显著增加GHV扩张,特别是在生殖中心B细胞.
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:
- 加玛疹病毒 (GHV) 是一种DNA瘤病毒,在淋巴细胞中产生终身潜伏感染.
- 病毒基因表达促进B细胞的增殖和分化,有助于病毒殖民.
- 对于病毒驱动的细胞扩张的宿主控制机制尚未完全理解.
研究的目的:
- 研究瘤抑制剂p53在控制马疹病毒诱导的B细胞在潜伏期扩张中的作用.
- 识别引发宿主抗增殖反应的病毒因素.
主要方法:
- 利用了小动物模型的玛疹病毒病原体.
- 在潜伏感染的B细胞中分析了p53的激活.
- 研究了M2基因和爱斯坦-巴尔病毒隐性膜蛋白1 (LMP1) 的功能.
主要成果:
- p53被激活在被鼠类马疹病毒68 (MHV-68) 感染的B细胞中.
- 缺少p53导致MHV-68延迟扩张的增加,特别是在生殖中心B细胞中.
- MHV-68 M2蛋白和EBV LMP1通过Src家族激酶诱导p53依赖的抗繁殖反应.
结论:
- p53作为一个关键的宿主防御作用,对抗马疹病毒驱动的B细胞增殖.
- 促进B细胞扩张的马疹病毒延迟程序可以触发由p53.3控制的异常增殖.
- 这突出了p53媒介控制玛疹病毒感染的保存机制.
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