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ZOOLOGICAL RESEARCH · 2021 · IF 4.56

Potential aquatic environmental risks of trifloxystrobin: Enhancement of virus susceptibility in zebrafish through initiation of autophagy

Huan Wang,Tian-Xiu Qiu,Jian-Fei Lu,Han-Wei Liu,Ling Hu,Lei Liu,Jiong Chen

Chronic pollution in aquatic ecosystems can lead to many adverse effects, including a greater susceptibility to pathogens among resident biota. Trifloxystrobin (TFS) is a strobilurin fungicide widely used in Asia to control soybean rust. However, it has the potential to enter aquatic ecosystems, where it may impair fish resistance to viral infections. To explore the potential environmental risks of TFS, we characterized the antiviral capacities of fish chronically exposed to TFS and subsequently infected with spring viraemia of carp virus (SVCV). Although TFS exhibited no significant cytotoxicity at the tested environmental concentrations during viral challenge, SVCV replication increased significantly in a time-dependent manner within epithelioma papulosum cyprini (EPC) cells and zebrafish exposed to 25 μg/L TFS. Results showed that the highest viral load was more than 100-fold that of the controls. Intracellular biochemical assays indicated that autophagy was induced by TFS, and associated changes included an increase in autophagosomes, conversion of LC3-II, accumulation of Beclin-1, and degradation of P62 in EPC cells and zebrafish. In addition, TFS markedly decreased the expression and phosphorylation of mTOR, indicating that activation of TFS may be associated with the mTOR-mediated autophagy pathway. This study provides new insights into the mechanism of the immunosuppressive effects of TFS on non-target aquatic hosts and suggests that the existence of TFS in aquatic environments may contribute to outbreaks of viral diseases.

CAS / MDL: 67-68-5
研究领域: 环境毒理学 · 水生生物学 · 病毒学 · 免疫学
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FISH & SHELLFISH IMMUNOLOGY · 2023 · IF 4.7

Application of rhein as an immunostimulant controls spring viremia of carp virus infection

Yan Zhou,Tian-Xiu Qiu,Huan Wang,Ling Hu,Lei Liu,Jiong Chen

In recent years, the exploration of natural compounds possessing both immunostimulatory and antiviral activities has attracted growing attention in aquaculture research. Consequently, the pursuit of identifying natural products exhibiting anti-SVCV potential as immunostimulants holds significant promise, offering a pathway to mitigate the economic ramifications inflicted by SVCV outbreaks in aquaculture settings. Among them, rhein emerges as a particularly compelling contender. Boasting a widespread distribution, well-established extraction methods, and multiple biological activities, it has exhibited the capacity to enhance the antiviral activity of host cells in vitro by blocking the viral internalization process, with a peak inhibition rate of 44.0%. Based on this intervention, rhein inhibited apoptosis and mitochondrial damage triggered by SVCV infection, ultimately producing a significant antiviral effect. Moving beyond the laboratory setting, rhein's efficacy translates effectively into in vivo scenarios. It has demonstrated substantial antiviral potency by increasing the expression of antiviral-related genes, most notably, retinoic acid-inducible gene I ( RIG-I ), interferon-φ ( IFN-φ ) and IFN-stimulated gene product 15 ( ISG15 ). In concert with this genetic modulation, rhein efficiently reduces the viral load, precipitating a consequential enhancement in the survival rate of SVCV-infected fish, elevating it to an encouraging 16%. In conclusion, the outcomes of our investigation offer a compelling testament to rhein's potential as a valuable immunomodulator in the battle against SVCV infections in aquaculture, and the remarkable attributes exhibited by rhein underscore its viability for future commercial deployment.

CAS / MDL: 67-68-5 478-43-3
研究领域: 水产养殖 · 免疫学 · 病毒学 · 药理学
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CELLULAR SIGNALLING · 2018 · IF 3.487

A new coumarin derivative plays a role in rhabdoviral clearance by interfering glycoprotein function during the early stage of viral infection

Wei-Chao Chen,Lei Liu,Yu-Feng Shen,Yang Hu,Fei Ling,Gao-Xue Wang,Bin Zhu

Coumarin forms an elite class of naturally occurring compounds that possess promising antiviral therapeutic perspectives. In this study, a coumarin derivative 7-[6-(2-methylimidazole) hexyloxy] coumarin (D5) was designed and synthesized to evaluate antiviral activity on a rhabdovirus , spring viraemia of carp virus (SVCV). Our results demonstrated that D5 had a robust antiviral activity with >90% inhibitory rate of SVCV expression in the host cells. And D5 significantly reduced viral-induced apoptosis and recovered virus-activated caspase-3/8/9 activities. Further data determined that SVCV could alter the cytoskeletal structure of EPC cells, characterized by a circumferential ring of microtubules and a disrupted microfilament organization, whereas cytoskeleton structure in D5-treated cells kept the normal morphology. Mechanistically speaking, D5 could interfere with SVCV replication inside or outside of cells through two different approaches. Before the process of virus entry into EPC cells, D5 had an impact on SVCV glycoprotein structure so as to disrupt viral binding to the cell surface or translocation to the cytosol. Another strategy for D5 to against SVCV was that D5 significantly suppressed SVCV-activated autophagy, which was beneficial for the host cells to restrict SVCV viral replication, accompanied by a higher phosphorylation of Akt-mTOR. In summary, our results revealed that D5 was effective in weakening SVCV infection and regulating SVCV-induced undesirable conditions, and this compound provided new therapeutic implications for the treatment of rhabdoviruses.

CAS / MDL: 93-35-6
研究领域: 病毒学 · 药理学 · 分子生物学
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AQUACULTURE · 2024 · IF 3.9

Inhibition of fish rhabdovirus demonstrates application prospect of two methylimidazole phenylpropanoid-based small molecules in aquaculture

Tian-Xiu Qiu,Huan Wang,Yang Hu,Li-Peng Shan,Guang-Lu Liu,Lei Liu,Jiong Chen

Aquaculture faces significant challenges, notably spring viremia of carp (SVC) caused by spring viremia of carp virus (SVCV), which is particularly devastating due to its high mortality rates and rapid transmission among fish populations. This study introduces two novel methylimidazole phenylpropanoid-based small molecules, LML1013 and LML1014, synthesized for combating SVCV in aquaculture environments. Comprehensive in vitro and in vivo evaluations demonstrated that these compounds have potent antiviral activities against SVCV. They effectively inhibited SVCV replication in epithelioma papulosum cyprinid (EPC) cells and significantly reduced mortality rates in infected juvenile common carp. Further analyses revealed that daily administration of these compounds not only blocked SVCV replication but also stimulated the innate immune responses of the fish, thereby enhancing their overall resistance to viral infection. Notably, the antiviral efficacy was observed in a dose- and time-dependent manner without inducing cytotoxic effects, emphasizing their therapeutic potential. The stability of LML1013 and LML1014 in aquacultural water and their ability to prevent horizontal viral transmission were also confirmed, further supporting their feasibility as treatment options in aquaculture. Overall, the development of LML1013 and LML1014 provides a promising strategy for controlling SVCV outbreaks and enhancing the sustainability of fish farming operations. This approach offers significant implications for improving aquaculture biosecurity and effectively managing viral disease threats.

研究领域: 水产养殖 · 病毒学 · 药理学 · 免疫学
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