RIKEN Center for
Integrative Medical Science
(IMS)(理化学研究所）

Nicholas Parrish

This collaborative research aims to elucidate a novel mechanism of heritable antiviral immunity in mammals. We previously found that the virus-derived sequences called endogenous bornavirus-like nucleoprotein elements (EBLNs) are transcribed and processed into PIWI-interacting RNAs (piRNAs), which are antisense relative to mRNAs of homologous virus called Borna disease virus (BoDV). Together with known functions of piRNAs to silence piRNA-complementary targets, we hypothesized that EBLN-derived piRNAs may target BoDV sequence and function as an antiviral mechanism against BoDV. To test the hypothesis, we engineered mutant mice lacking piRNA-generating EBLNs. Because EBLN sequences are not completely identical to currently-circulating BoDV strains, we also knocked-in modern BoDV sequence into piRNA-generating loci to generate new piRNAs that enable silencing of BoDV mRNAs. Using these genetically modified animals, we are establishing BoDV testis infection models to determine whether if EBLN-derived piRNAs are involved in antiviral RNA interference. Once mature, this could reveal a novel mechanism of germline-encoded immune memory in mammals.