小柯机器人

德国维尔茨堡大学Bhupesh K. Prusty、Lars Dölken等研究人员合作发现，疱疹病毒编码的miRNA对miRNA的加工选择性抑制。相关论文于2022年5月4日在线发表于国际学术期刊《自然》。

研究人员发现病毒的microRNA（miRNA）介导的对宿主miRNA加工的抑制是一种细胞机制，人类疱疹病毒6A（HHV-6A）利用这种机制破坏线粒体结构，逃避内在的宿主防御措施，并推动病毒感染从潜伏期转换到细胞期。研究人员证明，病毒编码的miR-aU14通过与各自的初级（pri）-miRNA发夹环的直接作用，选择性地抑制多个miR-30家族成员的加工。随后miR-30的丧失和miR-30-p53-DRP1轴的激活引发了线粒体结构的深刻破坏。这损害了I型干扰素的诱导，对生产性感染和病毒再激活都是必要的。miR-aU14的异位表达引发了病毒从潜伏期的重新激活，确定了病毒的miR-aU14是疱疹病毒细胞-潜伏期转换的一个容易成药的核心调节因子。

这些研究结果表明，miRNA介导的对miRNA加工的抑制代表了一种普遍的细胞机制，可以被利用来选择性地针对miRNA家族的个别成员。研究人员预计，针对miR-aU14将为预防HHV-6相关疾病中疱疹病毒的再激活提供新的治疗方案。

据悉，疱疹病毒已经掌握了宿主细胞的调节和免疫规避，从而增强生产性感染、终身潜伏和再激活。长久以来，人们一直在探索，但却没有明确的关系，在细胞分裂-潜伏转换和病毒的非编码RNA之间存在着一种关系。

附：英文原文

Title: Selective inhibition of miRNA processing by a herpesvirus-encoded miRNA

Author: Hennig, Thomas, Prusty, Archana B., Kaufer, Benedikt B., Whisnant, Adam W., Lodha, Manivel, Enders, Antje, Thomas, Julius, Kasimir, Francesca, Grothey, Arnhild, Klein, Teresa, Herb, Stefanie, Jrges, Christopher, Sauer, Markus, Fischer, Utz, Rudel, Thomas, Meister, Gunter, Erhard, Florian, Dlken, Lars, Prusty, Bhupesh K.

Issue&Volume: 2022-05-04

Abstract: Herpesviruses have mastered host cell modulation and immune evasion to augment productive infection, life-long latency and reactivation1,2. A long appreciated, yet undefined relationship exists between the lytic–latent switch and viral non-coding RNAs3,4. Here we identify viral microRNA (miRNA)-mediated inhibition of host miRNA processing as a cellular mechanism that human herpesvirus 6A (HHV-6A) exploits to disrupt mitochondrial architecture, evade intrinsic host defences and drive the switch from latent to lytic virus infection. We demonstrate that virus-encoded miR-aU14 selectively inhibits the processing of multiple miR-30 family members by direct interaction with the respective primary (pri)-miRNA hairpin loops. Subsequent loss of miR-30 and activation of the miR-30–p53–DRP1 axis triggers a profound disruption of mitochondrial architecture. This impairs induction of type I interferons and is necessary for both productive infection and virus reactivation. Ectopic expression of miR-aU14 triggered virus reactivation from latency, identifying viral miR-aU14 as a readily druggable master regulator of the herpesvirus lytic–latent switch. Our results show that miRNA-mediated inhibition of miRNA processing represents a generalized cellular mechanism that can be exploited to selectively target individual members of miRNA families. We anticipate that targeting miR-aU14 will provide new therapeutic options for preventing herpesvirus reactivations in HHV-6-associated disorders.

DOI: 10.1038/s41586-022-04667-4

Source: https://www.nature.com/articles/s41586-022-04667-4

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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