FISH & SHELLFISH IMMUNOLOGY
·
2026
·
IF 4.2
Xinyue Ren,Baiqiao Chen,Kai Luo,Yayan Zhou,Yuxi Wu,Mingming Jiang,Ziyi Zhang,Yinghao Zhang,Yuqing Lv,Yueling Zhang,Zhihong Zheng
WSSV induces glycolytic reprogramming and promotes hemocyanin lactylation in Litopenaeus vannamei. • Tip60, HDAC3 and SIRT2 coordinately regulate the lactylation state of hemocyanin during infection. • Hyperlactylated hemocyanin enhances WSSV attachment to hemocytes and promotes viral proliferation. White spot syndrome virus (WSSV) is a major pathogen in shrimp aquaculture, yet how virus-induced metabolic rewiring alters immune effector function remains poorly understood. Here, we show that WSSV infection in Litopenaeus vannamei induces a Warburg-like metabolic shift characterized by increased glucose uptake, transcriptional activation of glycolytic genes, lactate accumulation, and reduced acetyl-CoA levels. This metabolic state is accompanied by enhanced lactylation and reduced acetylation of hemocyanin, a major respiratory and immune protein in shrimp. Through transcriptome-guided candidate screening and in vivo RNA interference, we identify Tip60 as a positive regulator of hemocyanin lactylation, whereas HDAC3 and SIRT2 act as negative regulators. Functional assays further demonstrate that hemocyanin samples isolated from sodium L-lactate-injected shrimp exhibit enhanced capacities to increase cell-associated WSSV on hemocytes and promote viral proliferation. Together, these findings support a model in which WSSV hijacks host glycolytic reprogramming to reshape the post-translational modification landscape and convert hemocyanin into a proviral factor. This study establishes a non-histone lactylation mechanism in crustacean antiviral biology and identifies the Tip60/HDAC3/SIRT2 axis as a potential target for host-directed control of WSSV infection.
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DOI
高影响因子
AQUACULTURE
·
2025
·
IF 3.9
Cheng Chen,Yu Wang,Kai Hao,Zhe Zhao
White Spot Syndrome Virus (WSSV) poses a major challenge to crustacean aquaculture, causing White Spot Disease (WSD) and significant economic losses worldwide. Despite its high infectivity, effective control strategies for WSSV are still lacking. In this study, 30 medicinal plants were screened, and C. fraxini was identified as a strong inhibitor of WSSV proliferation. Its active compound, esculetin, demonstrated potent antiviral activity, achieving 98.56 % inhibition at 80 mg/kg. Further analysis showed that esculetin inhibits WSSV replication in a dose-dependent manner, reduces viral transcription, and improves the resilience of infected crayfish. In both prophylactic and therapeutic treatments, as well as cohabitation assays, esculetin significantly decreased pathogen loads and prevented inter-host transmission, underscoring its potential as an effective disease control strategy. Esculetin works through multiple mechanisms: it suppresses viral genes involved in WSSV transcription, disrupts the virus's ability to manipulate host immune signaling, and interferes with its replication cycle. Additionally, esculetin modulates key enzymes, stabilizes apoptotic pathways, and mitigates oxidative stress and inflammation caused by infection. By restoring proteostasis and boosting host defense, esculetin ultimately enhances crayfish resistance to WSSV. These findings shed light on the pharmacological properties of esculetin and provide a strong rationale for its development as a potential agent to control WSSV outbreaks, supporting the sustainability of crustacean aquaculture.
研究领域:
病毒学
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水产养殖
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抗病毒药理学
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分子生物学
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免疫学
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天然产物
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DOI
高影响因子
Viruses-Basel
·
2022
·Vol. 14
·期 12
·2731
·
IF 5.818
Xu Zhang,Li-Peng Shan,Qi Zhao,Lei Liu,Xu OuYang,Yang Hu,Chen-Jie Fei,Jiong Chen
An outbreak of white spot syndrome virus (WSSV) can hit shrimp culture with a devastating blow, and there are no suitable measures to prevent infection with the virus. In this study, the activity of active molecules from Chinese herbs against WSSV was evaluated and screened. Taxifolin had the highest rate (84%) of inhibition of the WSSV infection. The viral infectivity and genome copy number were reduced by 41% when WSSV virion was pretreated with taxifolin prior to shrimp infection. A continuous exchange of taxifolin significantly reduced the mortality of shrimp infected with WSSV. Due to the WSSV virion infectivity being affected by taxifolin, the horizontal transmission of the virus was blocked with an inhibition rate of up to 30%, which would further reduce the cost of a viral outbreak. Additionally, the viral genome copy number was also reduced by up to 63% in shrimp preincubated in taxifolin for 8 h. There may be a connection to the enhancement of innate immunity in shrimp that resulted in a 15% reduction in mortality for taxifolin-fed shrimp after the WSSV challenge. After dietary supplementation with taxifolin, the resistance of larvae to WSSV was improved, indicating that taxifolin may be a potential immunostimulant for shrimp to prevent WSD. Therefore, the results indicate that taxifolin has application potential for blocking a WSSV outbreak and reducing the loss of shrimp culture.Keywords:taxifolin;WSSV;antiviral;Chinese herbs;Litopenaeus vannamei
研究领域:
海洋生物学
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免疫学
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病毒学
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DOI
PubMed
高影响因子
CHEMOSPHERE
·
2021
·
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
JOURNAL OF FISH DISEASES
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2021
·Vol. 45
·期 2
·349-359
·
IF 2.767
Yang Hu,Lei Liu,Li-peng Shan,Jiong Chen
White spot syndrome virus (WSSV) is an important pathogen causing high mortality in the shrimp industry in aquaculture, yet there is no treatment available to date. In order to find a treatment against WSSV infection, this study examined the anti-WSSV activity of eight natural compounds using shrimp larvae as a model. Among the eight compounds, paeoniflorin showed the most obvious anti-WSSV effect, with a maximum protection efficiency of WSSV-infected shrimp >60% at 100 μM. Furthermore, pretreatment and post-treatment experiments revealed that paeoniflorin could prevent and treat WSSV infection in shrimp. The antiviral activity of paeoniflorin in aquaculture water decreased rapidly with time, and the results showed that the stable anti-WSSV activity of paeoniflorin could only remain in water for 1 day. Thus, the dosing pattern of continuous medication changes was evaluated. Obviously, in the model of continuous change of paeoniflorin, WSSV copy numbers in the virus-treated shrimp group still progressively increased, while the virus content in WSSV paeoniflorin -treated group continued to decrease. Interestingly, paeoniflorin inhibited horizontal transmission of WSSV to a certain extent. Notably, paeoniflorin significantly increased the expression of antimicrobial peptides of shrimp to resist WSSV. In conclusion, paeoniflorin has the potential to protect shrimp against WSSV.
研究领域:
水产养殖
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病毒学
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海洋生物学
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抗病毒研究
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天然产物
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DOI
高影响因子
AQUACULTURE
·
2022
·
IF 5.135
Jia Liu,Cheng Chen,Hui Du,Dexin Wang,Haixiang Ma,Gaoxue Wang,Tao Liu,Erlong Wang
White spot syndrome virus (WSSV), the causative agent of White spot disease (WSD), has caused high mortality and great economic losses in worldwide crustacean industries including shrimp and crayfish. Many bioactive components of Chinese herbs have been reported to be effective to control aquatic viral diseases including WSD. In this study, the antiviral effects of twelve herbal extracts were evaluated in WSSV-infected crayfish model, and Sophora flavescens extract exhibited the highest inhibition rate (87.63%) of WSSV replication. The anti-WSSV effect of matrine , the main bioactive component of S. flavescens, was further investigated. The results showed matrine could significantly inhibit WSSV replication in a dose-dependent manner and exhibited a robust inhibition rate (96.16%) with 50 mg/kg. Matrine both possessed potential preventive and therapeutic effects against WSSV infection and the preventive effect was better than the therapeutic effect. Besides, compared with the control, matrine significantly ( p < 0.01) improved the survival rate of WSSV-infected crayfish (from 0% to 48.57% on 10th day), notably ( p < 0.01) suppressed the expression of virus replication-related genes ie1 , DNApol and Vp28 , remarkably ( p < 0.01) activated C-type lectin ( CTL ) and prophenoloxidase ( ProPo ) and inhibited barrier-to-autointegration ( BAF ) expression to improve crayfish innate immunity against WSSV infection, up-regualated the CAT and GST expression and down-regulated the expression of NF-κB , cyclooxygenases COX-1 and COX-2 genes to balance the oxidative stress and inflammatory injury caused by WSSV. This study will provide a theoretical basis for the development of matrine as an efficient and practical anti-WSSV drugs and meaningful reference for the study of antiviral effect of matrine on other aquatic animal viruses.
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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DOI
高影响因子
AQUACULTURE
·
2026
·
IF 4.4
Cheng Chen,Yu-Jun Liu,Jing-Lei Shen,Tao Wang,Chang-Shuai Liang,Fei Ling,Gao-Xue Wang
A robust NSN-targeted screening platform for anti-WSSV discovery was developed. • The platform enables rapid and scalable identification of antiviral compounds. • Natural products with potent NSN inhibition were identified from a focused library. • Active compounds induced conformational changes in NSN structure. • The platform bridges biochemical screening with organism-level validation. White spot syndrome virus (WSSV), the etiological agent of white spot disease (WSD), causes rapid and high mortality in crustaceans and leads to severe economic losses in global aquaculture. The lack of permissive cell lines for WSSV propagation, together with the limitations of conventional in vivo screening approaches, has greatly constrained antiviral drug discovery. Here, we established a target-based in vitro screening platform focusing on the viral non-specific endonuclease (NSN), a key enzyme involved in WSSV replication. Recombinant WSSV-NSN was successfully expressed and purified, exhibiting a specific activity of 83.35 U/mg and a Michaelis constant (Km) of 106 mmol/L, with Mg 2+ as a strong activator. Based on enzymatic characterization, reaction conditions were optimized, and a robust screening system was developed with a Z′ factor of 0.70, indicating high reliability for high-throughput screening. Application of this platform to a natural compound library identified five NSN inhibitors, including luteolin, β-sitosterol, geniposide, cinnamic acid, and 1-hydroxyphenazine, with inhibition rates ranging from 58.5% to 96.6%. Enzyme kinetic inhibition analysis further showed that luteolin and β-sitosterol decreased Vmax with only minor changes in Km, suggesting that these compounds mainly reduced the catalytic capacity of NSN rather than simply competing with the RNA substrate. Circular dichroism analysis further revealed that luteolin and β-sitosterol directly interacted with NSN and induced conformational changes in its secondary structure, suggesting a potential mechanism of enzyme inhibition. Notably, representative compounds (luteolin and β-sitosterol) were further validated in vivo , where they significantly improved crayfish survival and reduced viral load following WSSV challenge, supporting the predictive capability of the NSN-targeted screening platform. Overall, this study establishes a reliable and efficient NSN-targeted screening system and demonstrates its effectiveness in identifying bona fide anti-WSSV agents, providing a practical strategy for target-based antiviral drug discovery in crustaceans.
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DOI
高影响因子
AQUACULTURE
·
2024
·
IF 3.9
Yaqi Zhao,Ting Xue,Jinwu Wang,Huarong Guo
Long-term in vitro cultured crayfish cells can serve as a valuable tool for investigating various aspects of crayfish biology, encompassing cell physiology and viral mechanisms. Regrettably, they are difficult to maintain a highly active state and survive during long-term and continuous culture in vitro . In order to generate highly viable crayfish cell cultures, it is crucial to optimize dependable culture conditions and utilize a suitable cell medium. In this study, we have successfully developed reliable in vitro long-term culture systems for hematopoietic (HPT) cells of crayfish Cherax quadricarinatus by formulating an optimal crayfish cell growth medium (OCCM), including under two-dimensional (2D) and three-dimensional (3D) conditions. The novel medium was optimized by a mix of exogenous nutrients, crayfish plasma (CP) and shrimp serum-derived amino acids and saccharides within the Leibovitz's L-15 (L-15) medium. Our newly developed crayfish cell growth medium (CCM-28) enabled the culturing of HPT cells for over 142 days under 2D and over 60 days under 3D conditions, with consistent active cell proliferation observed over a 30-day incubation period. This proliferation was comparable to in vivo conditions, with a cell division rate exceeding 20%, suggesting that a high mitotic rate has been successfully achieved during long-term in vitro culture. Flow cytometry analysis further elucidated the mitosis-arrest of HPT cells cultured in vitro was predominantly observed in the G 0 /G 1 phase. Furthermore, the cell subculture techniques have been established using mechanical dissociation method (in 2D) and substrate exchange method (in 3D). Additionally, the susceptibility of these cell cultures to covert mortality nodavirus (CMNV) and white spot syndrome virus (WSSV) was confirmed by capturing cytopathic effects (CPE) and analyzing viral copy numbers. Species identification using the cytochrome oxidase subunit I ( COI ) gene established the origin of the cell cultures from C. quadricarinatus . In conclusion, the successful development of highly viable crayfish cells in long-term in vitro culture systems, as demonstrated in this study, will significantly advance the research on immortalization in crayfish cells and the study of mechanisms related to viruses.
研究领域:
细胞生物学
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病毒学
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水产养殖
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海洋生物学
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产品关联
DOI
高影响因子
PLoS Pathogens
·
2022
·Vol. 18
·期 9
·e1010808
·
IF 7.464
Pan-Pan Hong,Cang Li,Guo-Juan Niu,Xiao-Fan Zhao,Jin-Xing Wang
Previous studies have shown that the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway has antiviral functions or is beneficial for viral replication, however, the detail mechanisms by which mTORC1 enhances viral infection remain unclear. Here, we found that proliferation of white spot syndrome virus (WSSV) was decreased after knockdown of mTor (mechanistic target of rapamycin) or injection inhibitor of mTORC1, rapamycin, in Marsupenaeus japonicus , which suggests that mTORC1 is utilized by WSSV for its replication in shrimp. Mechanistically, WSSV infects shrimp by binding to its receptor, polymeric immunoglobulin receptor (pIgR), and induces the interaction of its intracellular domain with Calmodulin. Calmodulin then promotes the activation of protein kinase B (AKT) by interaction with the pleckstrin homology (PH) domain of AKT. Activated AKT phosphorylates mTOR and results in the activation of the mTORC1 signaling pathway to promote its downstream effectors, ribosomal protein S6 kinase (S6Ks), for viral protein translation. Moreover, mTORC1 also phosphorylates eukaryotic translation initiation factor 4E-binding protein 1 (4EBP1), which will result in the separation of 4EBP1 from eukaryotic translation initiation factor 4E (eIF4E) for the translation of viral proteins in shrimp. Our data revealed a novel pathway for WSSV proliferation in shrimp and indicated that mTORC1 may represent a potential clinical target for WSSV control in shrimp aquaculture.
White spot syndrome virus (WSSV) is the causative pathogen of white spot disease (WSD) and represents the most destructive viral disease of shrimp. The virus has evolved various strategies to escape from host defenses or exploit host biological pathways for its reproduction. Studies on viral immune-escape mechanisms can provide new strategies for disease prevention and control in shrimp aquaculture. Mechanistic target of rapamycin (mTOR) plays a central role in the regulation of cell growth and metabolism, which nucleates two distinct protein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2) with diverse functions at different levels of the signaling pathway. mTORC1 is reported to be exploited by viruses in their reproduction. However, the detail mechanism remains unclear. In this study, we identified a new mechanism of mTOR being hijacked by WSSV in shrimp ( Marsupenaeus japonicus ). WSSV infects shrimp by its receptor, pIgR and induces the interaction of the intracellular domain of pIgR with Calmodulin. Calmodulin subsequently promotes the activation of AKT by interaction with the pleckstrin homology domain of the kinase. Activated AKT phosphorylates mTOR and results in the activation of the mTORC1 signaling pathway to promote its downstream effectors, S6Ks, for viral protein synthesis. Moreover, mTORC1 also phosphorylates 4EBP1, which results in the separation of 4EBP1 from eIF4E for the translation of viral proteins in shrimp. Our study reveals a novel strategy for WSSV proliferation in shrimp and indicates that the components of mTORC1 may represent potential clinical targets for WSSV control in shrimp aquaculture.
研究领域:
水产养殖
·
病毒学
·
分子生物学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
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