美国杜克大学医学院Z. Z. Zhao Zhang和Lu Wang共同合作，近期取得重要工作进展。他们研究发现果蝇变态过程中逆转录子的激活能为成体抗病毒反应提供条件。这一研究成果2022年11月17日在线发表于《自然—遗传学》杂志上。

研究人员发现，在特定的发育时间窗口内，逆转录转座子激活可以许可宿主的免疫系统进行未来的抗病毒反应。他们发现，mdg4（也称为Gypsy）反转录转座子在果蝇蛹阶段的变态过程中选择性地变得活跃。在这个阶段，mdg4激活通过以dSTING依赖的方式诱导核因子-κB蛋白Relish的全身抗病毒功能来培育宿主的先天免疫系统。因此，在蛹期沉默mdg4、Relish或dSTING的成虫无法清除外源病毒并容易感染病毒。总之，数据表明，由于移动基因元件的发育激活，宿主可以建立一种保护性抗病毒反应，这种反应在病原体战争中具有长期益处。

据介绍，逆转录转座子是一种可移动的遗传元素，它广泛存在于几乎所有动物的基因组中。它们不受控制的激活会导致不育、癌症和其他疾病，因此在很大程度上被认为是有害的。

附：英文原文

Title: Retrotransposon activation during Drosophila metamorphosis conditions adult antiviral responses

Author: Wang, Lu, Tracy, Lauren, Su, Weijia, Yang, Fu, Feng, Yu, Silverman, Neal, Zhang, Z. Z. Zhao

Issue&Volume: 2022-11-17

Abstract: Retrotransposons are one type of mobile genetic element that abundantly reside in the genomes of nearly all animals. Their uncontrolled activation is linked to sterility, cancer and other pathologies, thereby being largely considered detrimental. Here we report that, within a specific time window of development, retrotransposon activation can license the host’s immune system for future antiviral responses. We found that the mdg4 (also known as Gypsy) retrotransposon selectively becomes active during metamorphosis at the Drosophila pupal stage. At this stage, mdg4 activation educates the host’s innate immune system by inducing the systemic antiviral function of the nuclear factor-κB protein Relish in a dSTING-dependent manner. Consequently, adult flies with mdg4, Relish or dSTING silenced at the pupal stage are unable to clear exogenous viruses and succumb to viral infection. Altogether, our data reveal that hosts can establish a protective antiviral response that endows a long-term benefit in pathogen warfare due to the developmental activation of mobile genetic elements.

DOI: 10.1038/s41588-022-01214-9

Source: https://www.nature.com/articles/s41588-022-01214-9