Domestic chickens activate a piRNA defense against avian leukosis virus

Abstract

PIWI-interacting RNAs (piRNAs) protect the germ line by targeting transposable elements (TEs) through the base-pair complementarity. We do not know how piRNAs co-evolve with TEs in chickens. Here we reported that all active TEs in the chicken germ line are targeted by piRNAs, and as TEs lose their activity, the corresponding piRNAs erode away. We observed de novo piRNA birth as host responds to a recent retroviral invasion. Avian leukosis virus (ALV) has endogenized prior to chicken domestication, remains infectious, and threatens poultry industry. Domestic fowl produce piRNAs targeting ALV from one ALV provirus that was known to render its host ALV resistant. This proviral locus does not produce piRNAs in undomesticated wild chickens. Our findings uncover rapid piRNA evolution reflecting contemporary TE activity, identify a new piRNA acquisition modality by activating a pre-existing genomic locus, and extend piRNA defense roles to include the period when endogenous retroviruses are still infectious.DOI: http://dx.doi.org/10.7554/eLife.24695.001

Host–transposon interactions: conflict, cooperation, and cooption

“…Small RNA profiling also revealed abundant viral-derived piRNAs in Drosophila cell culture-thought to reflect naturally occurring infections (Wu et al 2010)-but not in actual flies subjected to experimental viral infection (Petit et al 2016). Chickens that harbor endogenized avian leukosis virus (ALV) sequences also produce copious amount of piRNAs from these loci in their testes (Sun et al 2017). Since one of these ALV loci, ALVE6, has been historically associated with ALV resistance (Robinson et al 1981), it is tempting to speculate that piRNAs derived from this locus offer antiviral protection.…”

Co-option of endogenous viral sequences for host cell function

“…For example, some EBLNs in rodents and primates appear to have inserted into piwi-interacting RNA (piRNA) genomic clusters and as a result produce piRNA-like RNAs in the testis [40]. Similarly, chickens also exhibit testis-specific piRNA expression, which appear to mostly map to young ALV derived ERV insertions, some of which are known to produce infectious viral particles [41]. It has been proposed that these small RNAs offer some protection to the host by silencing exogenous viral mRNAs [16,40,41].…”

“…Similarly, chickens also exhibit testis-specific piRNA expression, which appear to mostly map to young ALV derived ERV insertions, some of which are known to produce infectious viral particles [41]. It has been proposed that these small RNAs offer some protection to the host by silencing exogenous viral mRNAs [16,40,41]. It has also been reported that elevated levels of ERV-derived RNAs leads to the accumulation of cytosolic nucleic acids, including double-stranded RNAs and complementary DNAs, which are recognized by nucleic acid sensors that direct cells to mount an antiviral and inflammatory response [42–44].…”

Identification of substrates of the small RNA methyltransferase Hen1 in mouse spermatogonial stem cells and analysis of its methyl-transfer domain

“…However, SSCs are rare in the adult testis (less than 0.1%), and the changes of sncRNAs in the SSCs upon mHen1 knockout were completely masked by the signal from other abundant cells in the testis. To explore the mHen1 substrates in mouse SSCs, we carried out sodium periodate (NaIO 4 )-assisted deep sequencing, a method previously used to investigate piRNA methylation (26,27). We generated mHen1 knockout SSC lines by the CRISPR/Cas9 method as well as Mili (a piRNA-binding protein indispensable for piRNA biogenesis) knockout SSC lines ( Fig.…”