Zhao Zhang

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.

Transposons are thought to be largely suppressed under physiological conditions, ensuring that their mobilization is a rare event. By tracking mobilization, we show that during metamorphosis at the Drosophila pupal stage, the Gypsy retrotransposon selectively mobilizes in regenerating tissues. In the newly formed tissues, this wave of Gypsy activation primes the host’s innate immune system by inducing the production of a nti m icrobial p eptides (AMPs). Moreover, early immune-priming functions of Gypsy are essential for combating viral invasion in adult flies: flies with Gypsy being silenced at the pupal stage are unable to clear viruses and succumb to viral infection. Our data reveal that regulated activation of transposons during animal developmental endows a long-term benefit in pathogen warfare.