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BACKGROUND: Voltage‐dependent anion‐selective channels (VDACs) serve as pore proteins within the mitochondrial membrane, aiding in the regulation of cell life and cell death. Although the occurrence of cell death is crucial for defense against virus infection, the function played by VDAC in Bombyx mori, in response to the influence of Bombyx mori nucleopolyhedrovirus (BmNPV), remains unclear. RESULTS: BmVDAC was found to be relatively highly expressed both during embryonic development, and in the Malpighian tubule and midgut. Additionally, the expression levels of BmVDAC were found to be different among silkworm strains with varying levels of resistance to BmNPV, strongly suggesting a connection between BmVDAC and virus infection. To gain further insight into the function of BmVDAC in BmNPV, we employed RNA interference (RNAi) to silence and overexpress it by pIZT/V5‐His‐mCherry. The results revealed that BmVDAC is instrumental in developing the resistance of host cells to BmNPV infection in BmN cell‐line cells, which was further validated as likely to be associated with initiating programmed cell death (PCD). Furthermore, we evaluated the function of BmVDAC in another insect, Spodoptera exigua. Knockdown of the BmVDAC homolog in S. exigua, SeVDAC, made the larvae more sensitive to BmNPV. CONCLUSION: We have substantiated the pivotal role of BmVDAC in conferring resistance against BmNPV infection, primarily associated with the initiation of PCD. The findings of this study shine new light on the molecular mechanisms governing the silkworm's response to BmNPV infection, thereby supporting innovative approaches for pest biocontrol. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Molybdenum cofactor sulfurase (MoCoS) is a key gene involved in the uric acid metabolic pathway that activates xanthine dehydrogenase to synthesise uric acid. Uric acid is harmful to mammals but plays crucial roles in insects, one of which is the immune responses. However, the function of Bombyx mori MoCoS in response to BmNPV remains unclear. In this study, BmMoCoS was found to be relatively highly expressed in embryonic development, gonads and the Malpighian tubules. In addition, the expression levels of BmMoCoS were significantly upregulated in three silkworm strains with different levels of resistance after virus infection, suggesting a close link between them. Furthermore, RNAi and overexpression studies showed that BmMoCoS was involved in resistance to BmNPV infection, and its antivirus effects were found to be related to the regulation of uric acid metabolism, which was uncovered by inosine‐ and febuxostat‐coupled RNAi and overexpression. Finally, the BmMoCoS‐mediated uric acid pathway was preliminarily confirmed to be a potential target to protect silkworms from BmNPV infection. Overall, this study provides new evidence for elucidating the molecular mechanism of silkworms in response to BmNPV infection and new strategies for the prevention of viral infections in sericulture. [ABSTRACT FROM AUTHOR]

The white epidermis of silkworms is due to the accumulation of uric acid crystals. Abnormal silkworm uric acid metabolism decreases uric acid production, leading to a transparent or translucent phenotype. The oily silkworm op50 is a mutant strain with a highly transparent epidermis derived from the p50 strain. It shows more susceptibility to Bombyx mori nucleopolyhedrovirus (BmNPV) infection than the wild type; however, the underlying mechanism is unknown. This study analysed the changes in 34 metabolites in p50 and op50 at different times following BmNPV infection based on comparative metabolomics. The differential metabolites were mainly clustered in six metabolic pathways. Of these, the uric acid pathway was identified as critical for resistance in silkworms, as feeding with inosine significantly enhanced larval resistance compared to other metabolites and modulated other metabolic pathways. Additionally, the increased level of resistance to BmNPV in inosine‐fed silkworms was associated with the regulation of apoptosis, which is mediated by the reactive oxygen species produced during uric acid synthesis. Furthermore, feeding the industrial strain Jingsong (JS) with inosine significantly increased the level of larval resistance to BmNPV, indicating its potential application in controlling the virus in sericulture. These results lay the foundation for clarifying the resistance mechanism of silkworms to BmNPV and provide new strategies and methods for the biological control of pests. [ABSTRACT FROM AUTHOR]

BACKGROUND: Nucleopolyhedrovirus (NPV), one of the baculoviruses, is a promising biopesticide for pest control. Lepidopteran account for 70% of pests, therefore investigation on highly conserved genes associated with viral infections in the lepidopteran model, the silkworm, will serve as a valuable reference for improving the effectiveness of pest management. BmE74A is a member of the erythroblast transformation‐specific (ETS) family of transcription factors in Bombyx mori, which we previously found to be highly conserved and closely associated with BmNPV. This study aimed to elucidate the role of BmE74A in viral infection. RESULTS: A significantly high expression of BmE74A in eggs indicated its important role in embryonic development, as did relatively high expressions in the hemolymph and midgut. Significant differences in BmE74A expression in different resistant strains after BmNPV infection suggested its involvement as a response to viral infection. Moreover, RNA interference (RNAi) and overexpression experiments confirmed the important role of BmE74A in promoting viral infection. BmNPV infection was significantly suppressed and enhanced by BmE74A knockdown and overexpression, respectively. Besides, BmE74A was found to regulate the expression of BmMdm2 and Bmp53. Furthermore, the binding of ETS, the functional domain of BmE74A, to occlusion‐derived virus proteins was confirmed by far‐western blotting, and four viral proteins that may interact with ETS proteins were identified by mass spectrometry. Similarly, a homolog of BmE74A in Spodoptera litura was also found to be involved in larval susceptibility to BmNPV. CONCLUSION: BmE74A promotes BmNPV proliferation by directly interacting with the virus, which may be related to the suppression of the p53 pathway. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The widespread use of pyrethroid pesticides has brought serious economic losses in sericulture, but there is still no viable solution. The key to solving the problem is to improve silkworm resistance to pesticides, which depends on understanding the resistance mechanism of silkworms to pesticides. This study aimed to use transcriptomes to understand the underlying mechanism of silkworm resistance to fenpropathrin, which will provide a theoretical molecular reference for breeding pesticide-resistant silkworm varieties. In this study, the fat bodies of two strains with differential resistance after 12 h of fenpropathrin feeding were analyzed using RNA-Seq. After feeding fenpropathrin, 760 differentially expressed genes (DEGs) were obtained in the p50(r) strain and 671 DEGs in the 8y strain. The DEGs involved in resistance to fenpropathrin were further identified by comparing the two strains, including 207 upregulated DEGs in p50(r) and 175 downregulated DEGs in 8y. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that these fenpropathrin-related DEGs are mainly enriched in the metabolism and transporter pathways. Moreover, 28 DEGs involved in the metabolic pathway and 18 in the transporter pathway were identified. Furthermore, organic cation transporter protein 6 (BmOCT6), a transporter pathway member, was crucial in enhancing the tolerance of BmN cells to fenpropathrin. Finally, the knockdown of the expression of the homologs of BmOCT6 in Glyphodes pyloalis (G. pyloalis) significantly decreased the resistant level of larvae to fenpropathrin. The findings showed that the metabolism and transporter pathways are associated with resistance to fenpropathrin in silkworm, and OCT6 is an effective and potential target not only for silkworm breeding but also for pest biocontrol. In this study, BmOCT6 was identified as a potential target for silkworm molecular breeding and the pest biocontrol. [Display omitted] • This is the first systematic study of the mechanism of silkworm to fenpropathrin. • The metabolic and transporter pathways are associated with silkworm resistance. • OCT6 is a potential target for silkworm breeding and pest biocontrol. [ABSTRACT FROM AUTHOR]