AQUACULTURE
·
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
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产品关联
DOI
高影响因子
AQUACULTURE
·
2024
·
IF 3.9
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
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病毒学
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药理学
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免疫学
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DOI
高影响因子
AQUACULTURE
·
2025
·
IF 3.9
Jia-Cheng Qin,Xiao-Ping Tan,Ying-Jie Jin,Guang-Shuo Wang,Shen-Ye Qu,Peng-Fei Li,Gao-Xue Wang,Fei Ling
Fish iridoviruses, including the largemouth bass virus (LMBV) and Singapore grouper iridovirus (SGIV), pose severe threats to aquaculture industries, resulting in substantial economic losses. However, no effective treatments are currently available for these viruses, underscoring the critical need to develop high-efficacy therapeutic strategies. This study identified chlorchinaldol as a compound exhibiting significant anti-LMBV activity both in vitro and in vivo in largemouth bass ( Micropterus salmoides ). Results revealed that chlorchinaldol inhibited LMBV replication in Epithelioma papulosum cyprinid (EPC) cells with a half-maximal inhibitory concentration (IC 50 ) of 9.40 μM, while concurrently reducing viral titers and cytopathic effects (CPE). Mechanistic investigations demonstrated that chlorchinaldol does not directly disrupt LMBV virion integrity but interferes with viral adsorption to host cells and suppresses late-stage viral protein synthesis. Furthermore, chlorchinaldol exhibited both prophylactic and therapeutic efficacy, significantly mitigating LMBV-induced cellular damage. In in vivo experiments, chlorchinaldol administration reduced viral loads in infected organs, ameliorated histopathological damage, upregulated immune-related gene expression, and markedly enhanced survival rates in LMBV-infected largemouth bass. Notably, chlorchinaldol also demonstrated potent anti-SGIV activity in EPC cells, with an IC 50 of 10.01 μM and suppression of viral titers and CPE. These findings collectively establish chlorchinaldol, a quinoline derivative, as a broad-spectrum antiviral agent with substantial potential for aquaculture applications.
研究领域:
病毒学
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水产养殖
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药理学
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产品关联
DOI
高影响因子
VACCINE
·
2016
·
IF 3.413
Tengfei Ma,Yongxia Liu,Jia Cheng,Yanhan Liu,Wentao Fan,Ziqiang Cheng,Xudong Niu,Jianzhu Liu
To obtain an effective vaccine candidate against duck Tembusu viral (DTMUV) disease which causes egg-drop and great economical loss in the Chinese duck industry, liposome vaccines containing recombinant E protein were prepared and assessed in this study. The recombinant plasmid (PET28a-E) was constructed and transformed into BL21 (DE3) cells to produce E proteins. The recombinant E proteins were purified and entrapped by liposomes through reverse-phase evaporation. Eighty-four cherry valley ducks were randomly divided into seven groups and inoculated intramuscularly at one- or seven-day-old with liposomes-E protein or Freund's adjuvant-E protein vaccine. Blood samples were collected from the first week to the tenth week for serum antibody , plasma for viremia , as well as oropharyngeal and cloacal swabs for virus shedding analyses after being challenged with a 10 2.4 50% tissue culture infective dose (TCID 50 ) of duck Tembusu virus. Results showed that serum antibody level of the liposomes vaccine was higher than the Freund's adjuvant vaccine, and inoculating twice was superior to once; furthermore, the viremia and virus shedding tests also proved that the liposomes vaccine can provide complete protection against DTMUV challenge. These results demonstrated that the liposomes-E protein vaccine could be used as a potential candidate vaccine to prevent DTMUV infection in ducks.
研究领域:
兽医学
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病毒学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF INFECTIOUS DISEASES
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2008
·Vol. 197
·期 1
·117-125
·
IF 6.035
Michaëlsson Jakob,Long Brian R.,Loo Christopher P.,Lanier Lewis L.,Spotts Gerald,Hecht Frederick M.,Nixon Douglas F.
Natural killer (NK) cells are believed to play a role in human immunodeficiency virus type 1 (HIV-1) disease progression, and NK cell levels are reduced in individuals with chronic HIV-1 infection. Interleukin (IL)-2 therapy results in an expansion of CD4+ T cells as well as NK cells; however, little is known about the detailed effects of IL-2 therapy on NKcells in HIV-1 infection in general and in early infection in particular. Here, we investigated the effects of combined IL-2 therapy and antiretroviral therapy (ART) on the number, frequency, phenotype, and interferon (IFN)-γ production of NK cells in individuals with early HIV-1 infection. Patients randomized to receive combined ART and IL-2 therapy predominantly expanded CD56dim NK cells, and the expansion was greater than in patients randomized to receive ART alone. Importantly, NK cell receptor expression and IFN-γ production were maintained over time. This reconstitution ofNKcells may be useful in helping contain viremia if patients discontinue therapy or develop drug resistance.
研究领域:
免疫学
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病毒学
·
传染病学
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DOI
PubMed
高影响因子
ANTIVIRAL RESEARCH
·
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
·
药学
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病毒学
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
Microbiome
·
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
·
微生物学
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病毒学
·
鱼类健康
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DOI
PubMed
高影响因子
VETERINARY RESEARCH
·
2025
·Vol. 56
·期 1
·1-17
·
IF 3.5
Zhang Yanwei,Jia Zhao,Yuan Gaoliang,Chen Kangyong,Cen Jing,Wang Junya,Feng Hao,Adamek Mikolaj,Zou Jun
Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a group of 34–120 kDa nuclear proteins that have recently been reported to participate in virus replication. The hnRNP family contains approximately 20 members, including hnRNP A1, hnRNP A2, hnRNP A2B1, hnRNPC, hnRNPD and hnRNPK. HnRNPC plays important roles in RNA biology, including expression, stability, mRNA splicing, nonspecific sequence export and 3’-end processing; however, the mechanisms underlying hnRNPC regulatory roles are not fully understood. Here, we found that zebrafish hnRNPC promoted spring viraemia of carp virus (SVCV) replication by increasing the stability of SVCV phosphoprotein while inhibiting the K48-linked ubiquitination of virus phosphoprotein, thereby suppressing the type I interferon (IFN) response. Mechanistically, hnRNPC could interact with the mediator of IFN regulatory factor 3 activation (MITA) to activate K48-linked ubiquitination for MITA degradation through the C-terminal domain of hnRNPC. We also showed that human hnRNPC could interact with MITA and that the overexpression of human hnRNPC decreased MITA protein in HEK293 cells, suggesting that the negative regulatory effects of hnRNPC on the type I IFN response are evolutionarily conserved. Collectively, our data indicate that hnRNPC promotes virus replication by suppressing IFN production activated by MITA and increasing the availability of viral proteins. Our work reveals an evolutionarily conserved mechanism that controls the IFN-mediated antiviral response by a member of the hnRNP family in vertebrates.
研究领域:
病毒学
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免疫学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2024
·
IF 4.1
Yanwei Zhang,Jing Cen,Haixia Wu,Wa Gao,Zhiying Jia,Mikolaj Adamek,Jun Zou
HnRNP A/B belongs to the heterogeneous nuclear ribonucleoprotein (hnRNP) family and plays an important role in regulating viral protein translation and genome replication. Here, we found that overexpression of hnRNP A/B promoted Spring viremia of carp virus (SVCV) and Cyprinid herpesvirus 3 (CyHV3) replication. Further, hnRNP A/B was shown to act as a negative regulator of type I interferon (IFN) response. Mechanistically, hnRNP A/B interacted with MITA, TBK1 and IRF3 to initiate their degradation. In addition, hnRNP A/B bound to the kinase domain of TBK1, the C terminal domain of MITA and IAD domain of IRF3, and the RRM1 domain of hnRNP A/B bound to TBK1, RRM2 domain bound to IRF3 and MITA. Our study provides novel insights into the functions of hnRNP A/B in regulating host antiviral response.
研究领域:
分子生物学
·
病毒学
·
免疫学
·
鱼类病理学
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产品关联
DOI
PubMed
高影响因子
AQUACULTURE
·
2022
·
IF 5.135
Hui Liang,Yadong Xie,Yu Li,Mingxu Xie,Ming Li,Wei Zhou,Jie Chen,Zhen Zhang,Yalin Yang,Chao Ran,Zhigang Zhou
Spring viraemia of carp virus (SVCV) is a critical pathogen of cyprinids. In this study, we investigated the effects of mannan on the antiviral resistance of zebrafish and elucidated the underlying mechanisms. Zebrafish were fed with a control diet or diet supplemented with 0.2%, 0.4%, 0.6% and 0.8% of mannan for 2 weeks, and were challenged by SVCV. The intestinal microbiota was evaluated by 16S rRNA gene pyrosequencing . Zebrafish embryonic fibroblast (ZF4) cells were treated with mannan and were infected by SVCV, and the expression of antiviral genes was investigated. In addition, the effect of the in vitro culture supernatant of mannan-associated microbiota on SVCV infection was evaluated in ZF4 cells model. Results showed that dietary 0.2%, 0.4% and 0.6% mannan significantly improved the survival rate of zebrafish compared with the control group ( P < 0.05). Consistent with in vivo results, mannan significantly inhibited the replication of SVCV in ZF4 cells ( P < 0.05). Moreover, mannan inhibited the adsorption of SVCV to ZF4 cells ( P < 0.05). The expression of type I interferon (IFN) signaling pathway related genes, including IRF3 , IFNφ1, IFNφ2, IFNφ3 , and PKZ, was significantly increased in mannan treated cells versus control ( P < 0.05). Dietary mannan modulated gut microbiota, with enrichment of Proteobacteria and reduced abundance of Firmicutes , Actinobacteriota, and Fusobacteriota. Furthermore, the culture supernatant of mannan-associated microbiota significantly inhibited SVCV replication in ZF4 cells versus control microbiota counterpart ( P < 0.05). Initial evaluation suggests that the antiviral effect of culture supernatant of mannan-associated microbiota involves a heat stable component derived from the commensal bacteria. To sum up, our results indicate that the mannan enhanced the resistance of zebrafish against SVCV infection. The mechanism underlying the antiviral effect of mannan include enhancement of IFN signaling and inhibition of viral adsorption. Dietary addition of Mannan altered the structure of the intestinal microbiota of zebrafish, and the intestinal microbiota also contributed to the anti-viral effect of mannan.
研究领域:
水产养殖
·
免疫学
·
微生物学
·
病毒学
✓ 已验证
DOI
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
·
病毒学
·
免疫学
·
药理学
·
生物化学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-12
·
IF 14.7
Cui Zhanding,Liu Jinlong,Xie Chong,Wang Tao,Sun Pu,Wang Jinlong,Li Jiaoyang,Li Guoxiu,Qiu Jicheng,Zhang Ying,Li Dengliang,Sun Ying,Yin Juanbin,Li Kun,Zhao Zhixun,Yuan Hong,Bai Xingwen,Ma Xueqing,Li Pinghua,Fu Yuanfang,Bao Huifang,Li Dong,Zhang Qiang,Liu Zaixin,Cao Yimei,Zhang Jing,Lu Zengjun
Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) poses a major threat to the global swine industry, yet effective prevention and control measures remain elusive. This study unveils Nitazoxanide (NTZ) as a potent inhibitor of PRRSV both in vitro and in vivo. Through High-Throughput Screening techniques, 16 potential anti-PRRSV compounds are identified from a library comprising FDA-approved and pharmacopeial drugs. We show that NTZ displays strong efficacy in reducing PRRSV proliferation and transmission in a swine model, alleviating viremia and lung damage. Additionally, Tizoxanide (TIZ), the primary metabolite of NTZ, has been identified as a facilitator of NMRAL1 dimerization. This finding potentially sheds light on the underlying mechanism contributing to TIZ’s role in augmenting the sensitivity of the IFN-β pathway. These results indicate the promising potential of NTZ as a repurposed therapeutic agent for Porcine Reproductive and Respiratory Syndrome (PRRS). Additionally, they provide valuable insights into the antiviral mechanisms underlying NTZ’s effectiveness.
研究领域:
兽医学
·
分子生物学
·
药理学
·
病毒学
·
治疗学
✓ 已验证
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）