Germline piRNAs counteract endogenous retrovirus invasion from somatic cells.

Most Drosophila transposable elements (TEs) are LTR retrotransposons, some of which belong to the genus Errantivirus and share structural and functional characteristics with vertebrate endogenous retroviruses (ERVs). These virus-derived elements occupy a large part of the genome, but it is unclear whether and how they can be reactivated and if they retain their replication capacity. We created conditions where control of the Drosophila ZAM errantivirus through the piRNA pathway was abolished leading to its reactivation in real time in somatic gonadal cells. We show that ZAM may remain active in these cells indicating that errantiviruses may hide from the efficient germline piRNA pathway by being expressed exclusively in somatic cells. After reactivation, ZAM invaded the oocytes and severe fertility defects were observed. The germline then set up its own adaptive genomic immune response against the constantly invading errantivirus, restricting invasion and restoring fertility. Our results not only highlight how errantiviruses and their host adapt to each other but also reveal a time window during oogenesis that may be favourable for viral germline invasion and endogenization.