Lai Wenxuan, Xia Junmin, Fei Shigang, Zhou Minyang, Huang Yigui, Luo Wenjie, Kong Yibing, Swevers Luc, Sun Jingchen, Feng Min
Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, Guangdong Engineering Technology Research Center of Sericulture, College of Animal Science, South China Agricultural University, Guangzhou, China.
Insect Molecular Genetics and Biotechnology, National Centre for Scientific Research Demokritos, Institute of Biosciences and Applications, Athens, Greece.
Insect Biochem Mol Biol. 2025 Aug;182:104352. doi: 10.1016/j.ibmb.2025.104352. Epub 2025 Jun 23.
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.
一般认为，昆虫中不存在与干扰素信号系统同源的功能性抗病毒途径。然而，我们之前在蚕中鉴定出了一个干扰素刺激基因（ISG）同源基因BmCH25H，并揭示了BmCH25H依赖其羟化酶活性作为抗病毒效应因子。因此，我们推测蚕基因组中可能存在其他ISG同源基因，其中一些可能发挥抗病毒作用。在本研究中，基于对哺乳动物中ISG的了解，利用基因同源序列比对和保守结构域匹配方法，在蚕基因组中鉴定出了135个ISG同源基因。在这些蚕的ISG同源基因中，我们对一个重要的免疫转录因子——核因子白细胞介素3调节因子（NFIL3）进行了深入研究。我们的结果发现，BmNFIL3可以抑制家蚕核型多角体病毒（BmNPV）的增殖。此外，我们证实NFκ-B相关转录因子BmRelish受BmNFIL3调控，且其在BmNPV感染后的诱导是由BmNFIL3介导的。更重要的是，我们证明了BmNFIL3抗BmNPV的作用依赖于BmRelish。本研究首次对无脊椎动物中的ISG同源基因进行了系统鉴定，也是关于NFIL3在昆虫中具有抗病毒作用的首次报道。这些发现将为进一步了解昆虫的抗病毒免疫提供新的视角。
