Microbiome
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2024
·Vol. 12
·期 1
·1-19
·
IF 13.8
Zhang Yujun,Gao Yan,Li Chen,Zhang Yong-An,Lu Yuanan,Ye Jing,Liu Xueqin
Background Spring viremia of carp virus (SVCV) infects a wide range of fish species and causes high mortality rates in aquaculture. This viral infection is characterized by seasonal outbreaks that are temperature-dependent. However, the specific mechanism behind temperature-dependent SVCV infectivity and pathogenicity remains unclear. Given the high sensitivity of the composition of intestinal microbiota to temperature changes, it would be interesting to investigate if the intestinal microbiota of fish could play a role in modulating the infectivity of SVCV at different temperatures. Results Our study found that significantly higher infectivity and pathogenicity of SVCV infection in zebrafish occurred at relatively lower temperature. Comparative analysis of the intestinal microbiota in zebrafish exposed to high- and low-temperature conditions revealed that temperature influenced the abundance and diversity of the intestinal microbiota in zebrafish. A significantly higher abundance of Parabacteroides distasonis and its metabolite secondary bile acid (deoxycholic acid, DCA) was detected in the intestine of zebrafish exposed to high temperature. Both colonization of Parabacteroides distasonis and feeding of DCA to zebrafish at low temperature significantly reduced the mortality caused by SVCV. An in vitro assay demonstrated that DCA could inhibit the assembly and release of SVCV. Notably, DCA also showed an inhibitory effect on the infectious hematopoietic necrosis virus, another Rhabdoviridae member known to be more infectious at low temperature. Conclusions This study provides evidence that temperature can be an important factor to influence the composition of intestinal microbiota in zebrafish, consequently impacting the infectivity and pathogenicity of SVCV. The findings highlight the enrichment of Parabacteroides distasonis and its derivative, DCA, in the intestines of zebrafish raised at high temperature, and they possess an important role in preventing the infection of SVCV and other Rhabdoviridae members in host fish.
Video Abstract
研究领域:
水产养殖
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微生物学
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病毒学
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鱼类健康
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DOI
PubMed
高影响因子
AQUACULTURE
·
2024
·
IF 3.9
Yanzhi Yu,Yujun Zhang,Xiaojing Hua,Yuanan Lu,Xueqin Liu
Spring Viremia of Carp Virus (SVCV) is a highly pathogenic pathogen that infects carp fish, and SVCV infection frequently causes a severe inflammatory response in the affected fish. The viral infection is extremely lethal in carp larvae, often leading to heavy economic losses. Cholic acid (CA) is a primary bile acid synthesized directly from cholesterol in the liver and has been found to have an inhibitory effect on viral infections. To substantiate this antiviral potential, 500 μM CA was tested against SVCV replication in vitro and showed a significant inhibitory effect on viral replication. Further experimental tests demonstrated that CA exerted antiviral effects during its replication phase but not at viral adsorption and entry stages. In vivo experiments demonstrated that CA increased the survival rate of SVCV-infected zebrafish by 40 %, reduced viral load in tissues and reduced histopathological lesions. Comparison of the liver transcriptome of zebrafish between CA treatment and control (NC) groups revealed that CA treatment was able to promote the synthesis of polyunsaturated fatty acids, with the most significant changes in docosahexaenoic acid (DHA). Inhibition assay on fatty acid desaturase 2 (Fads2), the first rate-limiting enzyme for the synthesis of polyunsaturated fatty acid, showed that the antiviral effect of CA on SVCV disappeared. These new findings suggest that CA may exert its antiviral effects by regulating the synthesis of polyunsaturated fatty acid. In addition, this study also verified that DHA has antiviral activity against SVCV. In conclusion, CA shows promise as a potential anti-SVCV drug or feed additive that could help mitigate SVCV outbreaks in aquaculture.
研究领域:
水产养殖
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病毒学
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分子生物学
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免疫学
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产品关联
DOI
高影响因子
Cell Communication and Signaling
·
2026
·Vol. 24
·期 1
·191
·
IF 11.6
Zhao Zhao,Wei Xue-Feng,Zhao Liang,Xia Jun-Yao,Li Yu-Ya,Jia Yi-Jun,Zhu Bin
Background As the earliest vertebrates with innate and adaptive immunity, teleosts offer insights into the mammalian immune system. The intestine is the largest mucosal surface in the vertebrates and is a key immunological barrier contact with the external environment such as food, pathogens, and vaccine antigens. However, intestinal early immune responses post-vaccination remains unclear. This study aimed to explore intestinal vaccine uptake and early immune response mechanisms triggered by immunization. Methods In this study, we utilized zebrafish as a model for immersion immunization. We employed zebrafish as a model for immersion immunization. We immunized zebrafish by soaking them in a vaccine for 6 h, then transferred them to normal water for continued cultivation. We observed the uptake and absorption of the vaccine by the intestines after immunization through in vivo imaging and immunofluorescence. Additionally, transcriptomic analysis was conducted to identify the key signaling pathways and gene expression changes associated with the intestinal immune response. Results With the increase in immunization time, a significantly enhanced fluorescent signal can be observed in the intestine. The expression level of IgZ in the intestine was nearly 4 times that of the control group at 3 days post-vaccination (dpv), and the survival rate after challenge could reach 27.91%, which was significantly higher than that of the control group. Transcriptomic analysis revealed substantial upregulation of pathways involved in the p53 signaling pathway, antigen presentation, and T cell immune regulation post-vaccination. There is a marked reduction in the proportions of CD4 + and CD8α + T lymphocytes within the intestine of p53 mutant zebrafish. Conclusion Our research disclosed that p53 is involved in the early immune response by regulating antigen presentation and induces T-cell immune responses. This investigation provides novel insights and establishes a foundational understanding of early intestinal immune responses.
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DOI
高影响因子
JOURNAL OF VIROLOGY
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2026
·
IF 4.1
Huan Wang,Yang Hu,Lei Liu,Jiong Chen
Environmental pollutants are increasingly recognized as disease modifiers, reshaping host homeostasis and shifting host-pathogen dynamics toward higher infection risk in aquatic ecosystems. Here, we show that the widely used strobilurin fungicide trifloxystrobin (TFS) persistently erodes antiviral competence in fish and increases susceptibility to spring viremia of carp virus (SVCV) by driving dynamin-related protein 1 (Drp1)-mediated excessive mitophagy and sustained mitochondrial dysfunction. Using epithelioma papulosum cyprini (EPC) cells and zebrafish as complementary models, we find that environmentally plausible TFS exposures (2.5–25 μg/L) elevate SVCV permissiveness; notably, this phenotype resolves incompletely after chemical withdrawal. Transcriptomics revealed a dose-concordant shift toward stress/innate immune signaling and mitophagy programs, alongside broad repression of proliferative and DNA-repair pathways. Consistently, TFS induces persistent mitochondrial membrane depolarization, promotes fragmentation and ultrastructural deterioration, and increases mitochondria–lysosome coupling. Mechanistically, TFS elevates Drp1 abundance and Ser616 phosphorylation, promotes Drp1 recruitment to mitochondria, and sustains microtubule-associated protein 1 light chain 3B (LC3B)/lysosomal-associated membrane protein 2 (LAMP2) engagement, accompanied by persistent induction of core autophagy regulators (gabarap, atg5, wipi1, and ambra1) across extended recovery windows. In vivo, prolonged TFS exposure similarly yields durable enhancement of SVCV susceptibility even after long recovery periods, indicating incomplete restoration of host resistance. Together, these findings link a major agricultural fungicide to persistent Drp1-driven mitophagy overactivation and identify long-term antiviral resistance as an ecologically relevant endpoint for pesticide risk assessment and aquatic disease forecasting.
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DOI
PubMed
高影响因子
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
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2023
·
IF 2.9
Jiahong Guo,Wenji Huang,Xin Zhao,Ning Ji,Kangyong Chen,Yanjie Shi,Jianhua Feng,Jun Zou,Junya Wang
In mammals, interferon (IFN)-stimulated genes (ISGs) play important roles in restricting the replication of viruses . However, the functions of many ISGs have not been investigated in fish. In this study, eight isg12 homologs (termed isg12.1-8 ) were identified in zebrafish and all contain a typical ISG12 family domain rich of hydrophobic amino acid residues. Isg12.1-7 were significantly induced in the ZF4 cells by poly(I:C) and IFNφ1, and in the kidney and spleen after infection with spring viremia of carp virus (SVCV). In the EPC cells, overexpression of isg12.1 inhibited SVCV replication. Further, it was found that zebrafish ISG12.1 interacted with SVCV phosphoprotein (SVCV–P) and promoted SVCV-P degradation which could be attenuated by 3-MA and CQ (autophagy inhibitors). Our results indicate that zebrafish ISG12.1 restricts viral replication by targeting viral phosphoprotein for degradation.
研究领域:
分子生物学
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病毒学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AQUACULTURE
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2024
·
IF 3.9
Tian-Xiu Qiu,Lei Liu,Xu Zhang,Yang Hu,Jiong Chen
Isoliquiritigenin, a flavonoid from Glycyrrhiza glabra , demonstrates potent antiviral properties by enhancing host defenses through antioxidative and immunomodulatory mechanisms. Our in vitro data demonstrate that isoliquiritigenin significantly inhibits spring viremia of carp virus (SVCV) at concentrations up to 100 μg/ml without inducing cytotoxicity, effectively reducing viral replication and the production of new viral particles. Treatment with isoliquiritigenin markedly reduced the cytopathic effects in EPC cells, improving cell viability by more than 50 %. Furthermore, isoliquiritigenin enhances resistance to SVCV infection by significantly reducing intracellular the viral load when cells are pretreated for up to 24 h. This inhibition primarily occurs during the viral replication and assembly phases, without affecting viral binding or entry. Additionally, isoliquiritigenin strengthens antioxidant defenses and modulates immune responses, thereby reducing oxidative damage and interferon production. In vivo experiments with juvenile carp corroborate the antiviral efficacy of isoliquiritigenin, showing significantly reduced mortality rates and the viral load in SVCV-infected fish. These findings highlight the potential of isoliquiritigenin as an antiviral agent in aquaculture, providing a sustainable alternative to traditional chemotherapeutics by concurrently inhibiting viral replication and enhancing host immune defenses.
研究领域:
水产养殖学
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病毒学
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免疫学
✓ 已验证
产品关联
DOI
高影响因子
AQUACULTURE
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2025
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IF 3.9
Feiran Li,Guangyao Hu,Mengsha Zhou,Liqun Lu
Spring viremia of carp virus (SVCV) inflicts substantial economic damage on global cyprinid farming operations, primarily affecting common carp and koi carp. Currently, no effective control measures exist. Baicalein, a flavonoid derived from Scutellaria baicalensis , exhibits broad-spectrum antiviral activity. This study investigated baicalein's inhibitory effects against SVCV in vitro and in vivo. Cytotoxicity assays demonstrated no observable toxicity in EPC cells at concentrations of 1–25 μg/mL. Transcriptome analysis and biochemical assays revealed that baicalein enhances innate immunity via the NF-κB pathway while concurrently suppressing SVCV-induced apoptosis. In SVCV-infected koi, baicalein treatment significantly reduced viral replication, attenuated pathogenicity, and improved survival rates. Pharmacokinetic studies in koi carp indicated favorable properties: rapid absorption (Tmax = 4 h), sustained plasma presence (t 1/2 z/h > 7 h), and dose-proportional exposure (AUC 0-t ). These findings establish baicalein as a novel therapeutic candidate against SVCV in aquaculture.
研究领域:
水产养殖
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病毒学
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药理学
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鱼类健康
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抗病毒研究
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产品关联
DOI
高影响因子
FISH & SHELLFISH IMMUNOLOGY
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2020
·
IF 0
Chen Zhang,Sheng Guo,Zhao Zhao,Zi-Rao Guo,Rui Ma,Gao-Xue Wang,Bin Zhu
Spring viremia of carp virus (SVCV) causes devastating disease in aquaculture, resulting in significant economic impact. To develop an effective means against SVCV infection, a Lactococcus lactis ( L.lactis ) based subunit vaccine (pNZ-UGA) was developed based on surface displaying of SVCV glycoprotein using anchoring motif of the cA (C terminus of the peptidoglyvsn-binding) domains of AcmA, a major autolysin from L.lactis . The surface expression of SVCV glycoprotein was verified by indirect immunofluorescence assay. The efficacy of the constructed vaccine was further evaluated in common carp . The results showed that the higher levels of specific IgM could be detected in fish vaccinated with pNZ-UGA, compared with that in PBS and L.lactis groups. Immune-related genes including TNF-α , IL-6b , IL-1β , Cxcr 1 , Cxca , IFNg2b , I-IFN , and IgM expression in pNZ-UGA group were strongly up-regulated, revealing that robust innate immune response was induced. Notably, the lowest cumulative mortality (13.46%) was observed in fish vaccinated with pNZ-UGA vaccine after SVCV challenge, whereas the cumulative mortality were 100.00% and 92.31% in PBS and L.lactis groups, respectively. This study suggests the potential use of the recombinant L.lactis with surface displaying antigen proteins as effective vaccines against SVCV and other fish virus infection .
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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微生物学
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产品关联
DOI
PubMed
ANTIVIRAL RESEARCH
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2024
·
IF 4.5
Liang Zhao,Wei-Ze Wang,Tian-Tian Jiang,Tian-Zi Sun,Bo Liu,Bin Zhu
Spring viremia of carp virus (SVCV), as a high pathogenicity pathogen, has seriously restricts the healthy and sustainable development of cyprinid farming industry. In this study, we selected 5-Fluorouracil (5-Fu) as the drug model based on zeolitic imidazolate framework-8 (ZIF-8) to construct a drug delivery system (5-Fu@ZIF-8), and the anti-SVCV activity was detected in vitro and in vivo . The results showed 5-Fu@ZIF-8 was uniform cubic particle with truncated angle and smooth surface, and the particle size was 90 nm. The anti-SVCV activity in vitro results showed that the highest inhibition rate of 5-Fu was 77.93% at 40 mg/L and the inhibitory concentration at half-maximal activity (IC 50 ) was 20.86 mg/L. For 5-Fu@ZIF-8, the highest inhibition rate was 91.36% at 16 mg/L, and the IC 50 value was 5.85 mg/L. In addition, the cell viability was increased by 18.1% after 5-Fu treatment. Similarly, after 5-Fu@ZIF-8 treatment, the cell viability increased by 27.3%. Correspondingly, in vivo experimental results showed the viral loads reduced by 18.1% on the days 7 and the survival rate increased to 19.4% at 80 mg/L after 5-Fu treatment. For 5-Fu@ZIF-8, the viral loads reduced by 41.2% and the survival rate increased to 54.8%. Mechanistically, 5-Fu inhibits viral replication by regulating p53 expression and promoting early apoptosis in infected cells. All results indicated that 5-Fu@ZIF-8 improved the anti-SVCV activity; it may be a potential strategy to construct a drug-loaded system with ZIF-8 as a carrier for the prevention and treatment of aquatic diseases.
研究领域:
水产养殖
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药学
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病毒学
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纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
VIRUS RESEARCH
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2020
·
IF 2.934
Yu-Feng Shen,Yi-Hang Liu,Bo-Yang Li,Tian-Qiang Liu,Gao-Xue Wang
Rhabdoviruses cause devastating diseases in aquaculture, resulting in enormous economic losses. Our previous studies indicated that imidazole arctigenin derivatives possessed antiviral activities against aquatic rhabdoviruses. Based on the data of structure-activity relationship, a new imidazole arctigenin derivative, 4-(8-(2-bromoimidazole)octyloxy)-arctigenin (BOA), was designed and synthesized. And its antiviral activities against aquatic rhabdoviruses (SVCV, IHNV and MSRV) were evaluated in vitro . By comparing inhibitory concentration at half-maximal activity (IC 50 ), we found that BOA (IC 50 = 1.11 μM) possessed a higher anti-IHNV activity than the antiviral imidazole arctigenin derivatives which were found in our previous study. Besides, BOA could cause profound inhibition of SVCV and MSRV replication. By the reduction assays on cytopathic effect, BOA exhibited a protective effect on two host cell lines. As a typical rhabdovirus, SVCV was chosen as a model to illuminate the anti-rhabdovirus mechanism of BOA. BOA was discovered to not impact directly on viral particles or interfere with SVCV adsorption. And it worked within the 2−6 h of the early phase of virus replication. In addition, after repression of cell cycle S phase and recovery of caspase-3/8/9 activities activated by SVCV, BOA inhibited SVCV-induced apoptosis and then reduced the release of viral particles at the late stage of virus replication. Altogether, BOA was expected to be a highly efficient antiviral agent against multiple rhabdoviruses in the field of aquaculture.
研究领域:
水产养殖
·
病毒学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2018
·
IF 3.185
Yu-Feng Shen,Lei Liu,Chen-Zhang Feng,Yang Hu,Cheng Chen,Gao-Xue Wang,Bin Zhu
Coumarin as a lead structure have received a considerable attention in the last three decades for the discovery of antiviral agents. Our previous study indicated that imidazole coumarins possessed antiviral activities against SVCV . Based on the structure-activity relationship in that study, a new imidazole coumarin derivative, 7-(4-benzimidazole-butoxy)-coumarin (BBC), was designed, synthesized and its anti-SVCV activity was evaluated. By comparing inhibitory concentration at half-maximal activity (IC 50 ), we found that BBC (IC 50 = 0.56 mg/L) possessed a higher antiviral activity than those imidazole coumarins in our previous study. Besides, BBC can significantly inhibit cell death and reduce cellular morphological damage induced by SVCV. Our further data indicated that intraperitoneal injection of BBC increased the survival rate of zebrafish by 17.5%, decreased viral titer in fish body and inhibited SVCV glycoprotein expression in kidney and spleen . In uninfected zebrafish, the expression levels of ifnγ , ifnφ1 , ifnφ2 and rig1 genes were up-regulated after BBC treatment, which indicated that BBC could activate interferon response. In addition, data of the antioxidant enzymes activities and results of the antioxidant enzymes-related genes expressions suggested BBC could reduce SVCV-induced oxidative damage in infected zebrafish. Altogether, BBC is expected to be a therapeutic agent against SVCV infection in the field of aquaculture.
研究领域:
水产养殖
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病毒学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2024
·
IF 4.1
Tian-Xiu Qiu,Lei Liu,Huan Wang,Yang Hu,Jiong Chen
Spring viraemia of carp virus (SVCV) is a major threat to the aquaculture industry, causing severe economic losses and significantly impacting fish health. Despite this, no approved antiviral treatments are currently available for use in aquaculture, underscoring the urgent need for effective interventions. This study evaluated the antiviral and immunomodulatory potential of Schisandrin A (SA), a bioactive compound derived from the traditional Chinese medicinal herb Schisandra chinensis , against SVCV. Through a combination of in vitro and in vivo experiments, SA was found to significantly inhibit SVCV replication, lower the viral titer, and improve survival rates in infected juvenile carp. Mechanistically, SA enhanced the host’s innate immune response, as demonstrated by the upregulation of key antiviral genes including interferon-alpha1 ( ifna1 ), interferon-gamma ( ifnγ ), interferon-stimulated gene 15 ( isg15 ), and myxovirus resistance 1 ( mx1 ). Additionally, SA exhibited potent antioxidative properties, preserving mitochondrial integrity and reducing oxidative stress in SVCV-infected cells. These findings showed the dual role of SA in both directly suppressing viral replication and modulating the immune response, offering a multifaceted approach to managing SVCV infection. Given its low toxicity and biodegradability, SA emerges as a promising, sustainable antiviral agent for aquaculture. This study highlights the potential of SA to enhance biosecurity and promote sustainability in the industry, paving the way for the development of eco-friendly antivirals that could improve the management of viral diseases, ensuring healthier fish populations and greater economic stability.
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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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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