Identification of ISG homologous genes in silkworm and revelation of BmNFIL3 inhibition of BmNPV proliferation through regulation of BmRelish transcription.

It is generally believed that no functional antiviral pathway exists in insects, that is homologous to the interferon signaling system. However, we have previously identified an interferon-stimulated gene (ISG) homologous gene, BmCH25H, in the silkworm and revealed that BmCH25H relied on its hydroxylase activity as an antiviral effector. Therefore, we speculate that there may be additional ISG homologous genes in the silkworm genome, some of which may play an antiviral role. In this study, based on knowledge on ISGs in mammals, 135 ISG homologous genes were identified in the silkworm genome using gene homology sequence alignment and conserved domain matching methods. Among these ISG homologous genes in the silkworm, we conducted in-depth research on an important immunological transcription factor, nuclear factor interleukin 3 regulated (NFIL3). Our results found that BmNFIL3 could inhibit the proliferation of Bombyx mori nucleopolyhedrovirus (BmNPV). Furthermore, we confirmed that the NFκ-B-related transcription factor BmRelish was regulated by BmNFIL3 and that its induction after BmNPV infection was mediated by BmNFIL3. More importantly, we demonstrated that BmNFIL3 relied on BmRelish for its anti-BmNPV effects. This study represents the first systematic identification of ISG homologous genes in invertebrates and also constitutes the first report that NFIL3 has antiviral effects in insects. These findings will provide new perspectives for the further understanding of antiviral immunity in insects.