INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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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
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分子生物学
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病毒学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF VIROLOGY
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2025
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IF 3.8
Qisheng Qian,Shuang-shuang Zhao,Lei Yang,Guangxu Xing,Yumei Chen,Chao Liang,Haili Wang,Rui Li,Songlin Qiao,Aiping Wang,Gaiping Zhang
Porcine epidemic diarrhea (PED) is a highly pathogenic and infectious intestinal disease caused by the PED virus (PEDV) and has inflicted substantial economic losses on the global swine industry. Therefore, it is imperative to explore appropriate targets to restrain PEDV infection. PEDV spike (S) protein is crucial for viral infection and is regarded as an ideal target for the development of vaccines and antiviral therapeutics. Palmitoylation is a significant post-translational modification implicated in multiple viral replication cycles. Despite the fact that palmitoylation of certain coronavirus S proteins has been reported, the specific biological significance and underlying molecular mechanisms of PEDV S protein palmitoylation have not been fully defined. In the present study, we uncover that palmitoylation enhances the stability of PEDV S protein to promote viral proliferation. Mechanistically, we identify that a cysteine-rich region within the cytoplasmic tail of PEDV S protein is palmitoylated by the zinc finger Asp-His-His-Cys domain palmitoyltransferase 5 (ZDHHC5). We further illustrate that palmitoylation prevents the recognition of Lys-Phe-Glu-Arg-Gln (KFERQ)-like motif in PEDV S protein by heat shock cognate protein of 70 kDa (HSC70), thereby antagonizing its degradation via chaperone-mediated autophagy (CMA). Collectively, our findings underscore the importance of palmitoylation for PEDV pathogenesis and provide prospective targets for the development of antiviral interventions.
研究领域:
病毒学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
RESEARCH IN VETERINARY SCIENCE
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2017
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IF 1.298
Xiao-Bo Yu,Kai Hao,Jing Li,Xiao-Hui Chen,Gao-Xue Wang,Fei Ling
Moroxydine hydrochloride (Mor) and ribavirin (Rib) are known for their multi-antiviral activities against DNA and RNA viruses but little information is available about the pharmacological impact in aquaculture. The present study was undertaken to investigate the response of host cells to antiviral compounds during the anti-GCRV treatment. The scanning electron microscope results showed that Ctenopharyngodon idella kidney (CIK) cells have a higher death rate at 72 h post virus infection. At the concentration of 40 μg mL − 1 , Mor and Rib had a significant protective effect on virus-infected cells. Moreover, the gene expressions of vp5, vp6 and NS66 were significantly inhibited by treatment with Mor or Rib, especially gene expression of the vp5 . For the immunoregulatory action, no distinct induction of the expression of immune genes was observed after the addition of Mor and Rib to the virus-free cells. However, the compounds significantly decreased the virus-induced gene overexpression of Myd88, Mx1, IL-1β, IL-8, I-IFN and TNFα in CIK cells. Moreover, Mor and Rib significantly inhibited the immune genes upregulation which was induced by GCRV in kidney, liver, muscle and gill of grass carp, despite greater partial gene expressions were detected than the virus-free control group. Besides, Mor and Rib blocked cell cycle changes, cytopathic effects, cellular death and virus proliferation in CIK cells thereby maintaining normal morphological structure. Overall, Mor and Rib as antiviral compounds are effective for the control of GCRV replication and the indirectly regulation of cellular immune response.
研究领域:
水产养殖
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病毒学
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免疫学
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药理学
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产品关联
DOI
PubMed
高影响因子
CHEMOSPHERE
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2021
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IF 7.086
Hui Yang,Yinan Jiang,Kaiyuan Lu,Haoran Xiong,Yingying Zhang,Wenzhi Wei
Atrazine is considered as a potential environmental endocrine disruptors and exhibits various toxic effects on animals. It has a great impact in the aquatic ecosystems , but there are few studies on its immunotoxicity in crustaceans. In the present study, the Procambarus clarkii were utilized to assess the immune toxicity after 0.5 mg/L and 5 mg/L atrazine exposure. A significant decrease in total hemocytes count (THC) was observed at 5 mg/L atrazine exposure throughout the experiment. The activities of antioxidant enzymes including superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) were significantly inhibited, but the content of reactive oxygen species (ROS) and malondialdehyde (MDA) were up-regulated, indicating the potential oxidative stress . The analysis of the integrated biomarker response (IBR) showed the induction of oxidative stress biomarkers and the inhibition of antioxidants. After 5 mg/L atrazine exposure for 144 h, the integrity of crayfish hepatopancreas was destroyed with disappeared connections between tubules and increased liver tubules vacuoles. The relative expression levels of different immune genes in hepatopancreas after atrazine exposure were measured. Most of these genes were suppressed and exhibited a certain dose-dependent effect. The results of crayfish white spot syndrome virus (WSSV) replication shown the amount of virus in muscle was significantly higher and exhibited a higher mortality rate at 5 mg/L group than other groups. The present study determined the impact of atrazine exposure on WSSV outbreaks, and also provide an important basis for further assessing the occurrence of pesticides on diseases of P. clarkii.
研究领域:
环境科学
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水生毒理学
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免疫毒性学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）