INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
·
IF 8.5
Feng Chen,Mingyi Zhou,Wei Chen,Wenjing Geng,Liang Lu,Guanwang Shen,Ping Lin,Qingyou Xia,Ping Zhao,Zhiqing Li
N6-methyladenosine (m6A) is the most prevalent internal modification on mRNA and plays critical roles in various biological processes including virus infection. It has been shown that m6A methylation is able to regulate virus proliferation and host innate immunity in mammals and plants, however, this antiviral defense in insects is largely unknown. Here we investigated function of m6A and its associated methyltransferases in nucleopolyhedrovirus (BmNPV) infection in silkworm. We reported significant changes of m6A methyltransferases METTL3 and METTL14 upon BmNPV treatment. Knockdown of METTL3 and METTL14 enhanced BmNPV infection and promoted viral proliferation, whereas overexpression of these enzymes could prevent viral replication. Further study revealed that host heat shock cognate 70 ( Hsc70 ) as a target gene of m6A would contribute to BmNPV proliferation. CRISPR-dCas9-targeted methylation of Hsc70 by METTL3/METTL14 decreased its expression and further attenuated BmNPV infection. Consistently, knockout of METTL3 in silkworm individuals by CRISPR-Cas9 reduced overall m6A levels, which led to rapid death of silkworms and increase of BmNPV upon virus infection likely due to upregulated expression of Hsc70 . Collectively, these findings provided a novel insight into antiviral activity of m6A and demonstrated a distinct immune response via attenuating host Hsc70 expression to counteract BmNPV replication in lepidopteran silkworm.
CAS / MDL:
研究领域:
昆虫学
·
分子生物学
·
病毒学
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产品关联
DOI
PubMed
高影响因子
INSECT MOLECULAR BIOLOGY
·
2024
·
IF 2.3
Hui-Hua Cao,Wei-Wei Kong,Xi-Ya Chen,Sadaf Ayaz,Cai-Ping Hou,Yi-Sheng Wang,Shi-Huo Liu,Jia-ping Xu
The RNA interference pathway mediated by microRNAs (miRNAs) is one of the methods to defend against viruses in insects. Recent studies showed that miRNAs participate in viral infection by binding to target genes to regulate their expression. Here, we found that the Bombyx mori miRNA, miR-6498-5p was down-regulated, whereas its predicted target gene pyridoxal phosphate phosphatase PHOSPHO2 ( BmPLPP2 ) was up-regulated upon Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Both in vivo and in vitro experiments showed that miR-6498-5p targets BmPLPP2 and suppresses its expression. Furthermore, we found miR-6498-5p inhibits BmNPV genomic DNA (gDNA) replication, whereas BmPLPP2 promotes BmNPV gDNA replication. As a pyridoxal phosphate (PLP) phosphatase (PLPP), the overexpression of BmPLPP2 results in a reduction of PLP content, whereas the knockdown of BmPLPP2 leads to an increase in PLP content. In addition, exogenous PLP suppresses the replication of BmNPV gDNA; in contrast, the PLP inhibitor 4-deoxypyridoxine facilitates BmNPV gDNA replication. Taken together, we concluded that miR-6498-5p has a potential anti-BmNPV role by down-regulating BmPLPP2 to modulate PLP content, but BmNPV induces miR-6498-5p down-regulation to promote its proliferation. Our findings provide valuable insights into the role of host miRNA in B. mori –BmNPV interaction. Furthermore, the identification of the antiviral molecule PLP offers a novel perspective on strategies for preventing and managing viral infection in sericulture.
研究领域:
分子生物学
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病毒学
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昆虫学
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RNA干扰
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DOI
PubMed
高影响因子
INSECT MOLECULAR BIOLOGY
·
2023
·
IF 2.6
Zhi-hao Su,Jun-li Lv,Qi Ou,Zi-qin Zhao,Kai-yi Zheng,Xiao-ying Zhang,Wen-qing Lai,Xue-yang Wang,Ming-jie Deng,Mu-wang Li
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.
研究领域:
昆虫学
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分子生物学
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病毒学
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代谢组学
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DOI
PubMed
高影响因子
Biomolecules
·
2026
·Vol. 16
·期 6
·890
·
IF 5.6
Xiaoyu Sun,Chunguang Cui,Guangrong Huang,Xiaoli Zou,Shaofang Yu,Xin Du,Xia Xu,Jine Chen,Xingjian He,Yongqiang Wang,Linbao Zhu
C-type lectins (CTLs) are proteins with carbohydrate-recognition domains. These macromolecules interact with pathogen components, thereby playing important roles in the immune system. Current studies indicate that silkworm CTLs are involved inBombyx morinucleopolyhedrovirus (BmNPV) infection. Nevertheless, the molecular mechanisms through which these CTLs affect viral infection remain unclear. In this study,B. mori C-type lectin 16(BmCTL16) was identified in the silkworm. Its expression was significantly downregulated upon BmNPV infection. Functional assays showed that BmCTL16 overexpression suppressed BmNPV proliferation, whereas its knockdown enhanced BmNPV proliferation. Protein–protein interaction assays confirmed that BmCTL16 interacts with BmNPV protein Bm9 in the cytoplasm. Notably, BmCTL16 promoted the degradation of Bm9 via the ubiquitin–proteasome system. Knockdown of Bm9 by siRNA significantly reduced BmNPV proliferation, confirming that Bm9 is the key target for BmCTL16 to exert its antiviral function. Collectively, this study reveals a novel CTL-mediated antiviral mechanism. BmCTL16 interacts with Bm9 and promotes its ubiquitin–proteasome degradation, thereby inhibiting viral proliferation. Furthermore, BmNPV evades this host defense by downregulating BmCTL16 expression. These findings enhance our understanding of silkworm CTL-mediated antiviral defense and offer novel perspectives on host–virus interactions inB. mori.
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PubMed
高影响因子
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