干扰素诱导的circRNAs逃脱了疹病毒宿主关闭,并抑制了Lytic感染
Sarah E Dremel1, Takanobu Tagawa1, Vishal N Koparde2,3
1HIV and AIDS Malignancy Branch, National Cancer Institute, Bethesda, MD, United States.
bioRxiv : the preprint server for biology
|October 27, 2023
概括
干扰素诱导的循环RNAs (circRNAs) 抵抗疹病毒的降解,提供一种新的抗病毒防御. 这些circRNAs在病毒感染降解宿主信使RNA时提供了关键的防御机制.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 干扰素刺激的基因是关键的抗病毒防御.
- 疹病毒通过降解细胞RNA来抵消宿主防御.
- 循环RNA (circRNAs) 是一种具有新兴调节作用的非编码RNA类.
研究的目的:
- 为了研究干扰素诱导的circRNAs对疹病毒介导的降解的敏感性.
- 为了确定circRNAs是否对疹病毒具有抗病毒活性.
- 探索circRNAs作为泛疹病毒抗病毒策略的潜力.
主要方法:
- 在不同的疹病毒亚家族 (α,β,gamma) 中进行circRNA表达的比较.
- 宫外表达测试使用疹病毒内啡核酸酶.
- 干扰素-β和-γ治疗以评估circRNA调节.
- 对特定circRNAs (例如,circRELL1) 的功能的增益和损失研究.
主要成果:
- 作为一个群体,circRNAs对疹病毒诱导的宿主关闭具有抗性.
- 十个circRNAs在Lytic感染期间通常在人类疹病毒亚家族中受到调节.
- 干扰素刺激上调67个circRNAs,其中许多在感染期间也被上调.
- 干扰素刺激的circRNA,circRELL1,显示出对性HSV-1和KSHV感染的抑制作用.
结论:
- 干扰素诱导的circRNAs代表了对疹病毒感染的强有力的防御,逃避病毒降解.
- circRELL1表现出泛疹病毒抗病毒活性,突出其治疗潜力.
- 提出了一种双重抗病毒策略,涉及干扰素刺激基因的mRNA和circRNA产物.
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