Frontiers in Microbiology
·
2019
·
IF 4.259
Xue Biyun,Hou Gaopeng,Zhang Guixi,Huang Jingjing,Li Liangliang,Nan Yuchen,Mu Yang,Wang Lizhen,Zhang Lu,Han Ximeng,Ren Xiaolei,Zhao Qin,Wu Chunyan,Wang Jingfei,Zhou En-Min
Prevention and control of infection by porcine reproductive and respiratory syndrome virus (PRRSV) remains a challenge, due to our limited understanding of the PRRSV invasion mechanism. Our previous study has shown that PRRSV glycoprotein GP5 interacts with MYH9 C-terminal domain protein (PRA). Here we defined that the first ectodomain of GP5 (GP5-ecto-1) directly interacted with PRA and this interaction triggered PRA and endogenous MYH9 to form filament assembly. More importantly, MYH9 filament assembly was also formed in GP5-ecto-1-transfected MARC-145 cells. Notably, PRRSV infection of MARC-145 cells and porcine alveolar macrophages also induced endogenous MYH9 aggregation and polymerization that were required for subsequent PRRSV internalization. Moreover, overexpression of S100A4, a MYH9-specific disassembly inducer, in MARC-145 cells significantly resulted in diminished MYH9 aggregation and marked inhibition of subsequent virion internalization and infection by both PRRSV-1 and PRRSV-2 isolates. The collective results of this work reveal a novel molecular mechanism employed by MYH9 that helps PRRSV gain entry into permissive cells.
研究领域:
病毒学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF VIROLOGY
·
2025
·
IF 3.8
Xiaohan Chen,Yipeng Pang,Fructueux Modeste Amona,Zilu Liu,Fang Wang,Yuan Liang,Jiachen Yang,Wanhan Zhang,Xingtang Fang,Xi Chen
Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly contagious pathogen that causes substantial economic losses in the global swine industry, primarily by impairing reproductive performance and respiratory health. However, current therapeutic approaches remain limited in effectively controlling PRRSV infection. Here, we present self-assembled cyanidin-3-O-glucoside (C3G)-based nanoparticles (C3G-Cs-SeNPs) as a promising antiviral agent against PRRSV infection. These nanoparticles demonstrated excellent stability and biocompatibility, with minimal cytotoxicity in Marc-145 cells. C3G-Cs-SeNPs significantly reduced ROS levels in PRRSV-infected cells, enhancing the antioxidant capacity and mitigating oxidative stress. In addition, they effectively inhibited key stages of the PRRSV lifecycle, including viral internalization and replication, leading to a marked decrease in viral proliferation. Moreover, C3G-Cs-SeNPs alleviated ferroptosis by restoring redox homeostasis through enhanced antioxidant enzyme activity. Mechanistically, these nanoparticles potentially activate the SIRT1/Nrf2/HO-1 signaling pathway, which plays a critical role in regulating inflammation and ferroptosis in PRRSV-infected cells. These findings suggest that C3G-Cs-SeNPs could serve as a novel therapeutic approach to modulate inflammation, ferroptosis, and viral replication in respiratory viral infections. Our study highlights the therapeutic potential of C3G-Cs-SeNPs in combating PRRSV infection, with important implications for viral infection management and respiratory disease treatment.
研究领域:
病毒学
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纳米技术
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免疫学
·
抗病毒治疗
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氧化应激研究
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产品关联
DOI
PubMed
高影响因子
Progress in Natural Science-Materials International
·
2022
·
IF 4.269
Xue Li,Jinhua Li,Wentao Yang,Dandan Han,Na Yao,Hongbin Zhao,Xueying Chu,Xuemei Liang,Chunguang Bi,Chunfeng Wang,Guilian Yang
An ultrasensitive and selective sandwich-type fluorescent immunosensor based on fluorescence resonance energy transfer (FRET) between CdSe/ZnS quantum dots (QDs) and Au nanorods (AuNRs) was developed for the rapid detection of porcine reproductive and respiratory syndrome virus (PRRSV). Modified CdSe/ZnS QDs and AuNRs were bioconjugated with primary antibodies M and GP5, respectively. When the target antigen was present, a well-known sandwich-type form CdSe/ZnS QDs-M antibody-antigen-GP5 antibody-AuNRs was produced, and thus reducing the distance between the QDs and NRs. As a result, FRET occurred and the fluorescence intensity of CdSe/ZnS QDs decreased, and this decrease was used to determine the antigen concentration. Ultrasensitive detection of PRRSV at low concentrations in swine serum was achieved with a limit of detection of 0.55 TCID 50 /mL and a linear detection range of 10 1 –3.5 × 10 4 TCID 50 /mL. Therefore, the fluorescent immunosensor is selective and highly sensitive; specifically, it can detect PRRSV at low concentrations in swine serum over a large concentration range. This proposed detection method can facilitate the development of high-performance fluorescent immunosensors for the detection of PRRSV and other antigens.
研究领域:
生物传感器
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纳米技术
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病毒学
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兽医学
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产品关联
DOI
高影响因子
Frontiers in Nutrition
·
2025
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IF 5.1
Zhanding Cui,Jinlong Liu,Jinlong Wang,Jing Zhang,Yimei Cao,Kun Li,Zhixun Zhao,Hong Yuan,Xingwen Bai,Xueqing Ma,Pinghua Li,Yuanfang Fu,Huifang Bao,Dong Li,Qiang Zhang,Zaixin Liu,Kai Li,Tong Xu,Zengjun Lu
This study delves into the antiviral efficacy of Formononetin (FMN) and Mizoribine (MZR) against the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), a virus with a considerable economic impact and a current void in effective treatments. FMN and MZR were found to inhibit various PRRSV strains in vitro, predominantly in the early stages of viral infection. Noteworthy was the observation of their synergistic effects when combined with Ribavirin. The study underscores the antiviral potential of FMN and MZR, particularly emphasizing their low cytotoxicity at specific concentrations. These results position FMN and MZR as promising antiviral agents against PRRSV, underscoring their low cytotoxicity and efficacy in early-stage viral inhibition. Such findings pave the way for their potential inclusion in future PRRSV management strategies.
研究领域:
兽医学
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病毒学
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药理学
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产品关联
DOI
PubMed
高影响因子
Small
·
2020
·Vol. 16
·期 13
·1906206
·
IF 11.459
Ting Tong,Hongwei Hu,Junwei Zhou,Shuangfei Deng,Xiaotong Zhang,Wantao Tang,Liurong Fang,Shaobo Xiao,Jiangong Liang
With the gradual usage of carbon dots (CDs) in the area of antiviral research, attempts have been stepped up to develop new antiviral CDs with high biocompatibility and antiviral effects. In this study, a kind of highly biocompatible CDs (Gly-CDs) is synthesized from active ingredient (glycyrrhizic acid) of Chinese herbal medicine by a hydrothermal method. Using the porcine reproductive and respiratory syndrome virus (PRRSV) as a model, it is found that the Gly-CDs inhibit PRRSV proliferation by up to 5 orders of viral titers. Detailed investigations reveal that Gly-CDs can inhibit PRRSV invasion and replication, stimulate antiviral innate immune responses, and inhibit the accumulation of intracellular reactive oxygen species (ROS) caused by PRRSV infection. Proteomics analysis demonstrates that Gly-CDs can stimulate cells to regulate the expression of some host restriction factors, including DDX53 and NOS3, which are directly related to PRRSV proliferation. Moreover, it is found that Gly-CDs also remarkably suppress the propagation of other viruses, such as pseudorabies virus (PRV) and porcine epidemic diarrhea virus (PEDV), suggesting the broad antiviral activity of Gly-CDs. The integrated results demonstrate that Gly-CDs possess extraordinary antiviral activity with multisite inhibition mechanisms, providing a promising candidate for alternative therapy for PRRSV infection.
研究领域:
生物医学
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病毒学
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药理学
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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
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分子生物学
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药理学
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病毒学
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治疗学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2022
·
IF 7.033
Chunyan Shao,Ziwei Yu,Tongwang Luo,Bin Zhou,Quanjiang Song,Zhuoyue Li,Xiaoqiang Yu,Sheng Jiang,Yingshan Zhou,Wanyu Dong,Xingdong Zhou,Xiaodu Wang,Houhui Song
Introduction Porcine reproductive and respiratory syndrome virus (PRRSV) is a highly prevalent and endemic swine pathogen that causes significant economic losses to the global swine industry. Selenium nanoparticles (SeNPs) have attracted increasing attention in the biomedical field, given their antiviral effects. This study aimed to investigate the inhibitory effect of chitosan-coated SeNPs (CS-SeNPs) on PRRSV replication. Methods In this study, CS-SeNPs were synthesized by chemical reduction and characterized by assessing the morphology, size distribution, zeta potential, and element composition. Marc-145 cells were infected with r-PRRSV-EGFP (0.1 MOI) and inoculated with CS-SeNPs (10 μM). Subsequently, the concentrations of hydrogen peroxide (H 2 O 2 ) and glutathione (GSH), and glutathione peroxidase (GSH-Px) activity were measured using specific commercial assay kits. ORF5 RNA expression, viral titer, and nucleocapsid (N) protein expression were assessed using qRT-PCR, TCID 50 , and Western blot. ROS generation, apoptosis rates, and JNK /caspase-3/PARP protein expression were evaluated using dihydroethidium staining, flow cytometry, and Western blot. Results The results showed that CS-SeNPs treatment significantly suppressed oxidative stress induced by r-PRRSV-EGFP infection by increasing GSH-Px activity, promoting GSH production, and inhibiting H 2 O 2 synthesis. CS-SeNPs treatment significantly inhibited ORF5 gene expression, viral titers, and N protein of r-PRRSV-EGFP at 24 and 48 hours post-infection (hpi) in Marc-145 cells. The increase in apoptosis rates induced by r-PRRSV-EGFP infection was significantly decreased by CS-SeNPs inoculation through inhibiting ROS generation, JNK phosphorylation levels, and cleavage of caspase-3 and PARP mainly at 48 hpi. Conclusion These results demonstrated that CS-SeNPs suppress PRRSV-induced apoptosis in Marc-145 cells via the ROS/JNK signaling pathway, thereby inhibiting PRRSV replication, which suggested the potential antiviral activity of CS-SeNPs that deserves further investigation for clinical applications.
研究领域:
兽医学
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纳米技术
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病毒学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Integrative Agriculture
·
2017
·
IF 1.042
Feng ZHANG,Peng GAO,Xin-na GE,Lei ZHOU,Xin GUO,Han-chun YANG
Porcine reproductive and respiratory syndrome virus (PRRSV) actively induces cell apoptosis both in vitro and in vivo , which can contribute critically to viral pathogenesis. Previous studies have shown that the PRRSV nonstructural protein 4 (nsp4) is an important mediator of this process, but the underlying molecular details remain poorly understood. In this study, we found that the PRRSV nsp4 interacted with the mitochondrial inner membrane protein cytochrome c1 (cyto.c1) and induced its proteolytic cleavage. Interestingly, the cleaved N-terminal fragment of cyto.c1 was found to exert apoptotic activity, which could cause mitochondrial fragmentation, resulting in apoptotic cell death. And RNA interference (RNAi) silencing experiments further confirmed the crucial role which cyto.c1 played in nsp4- and PRRSV-induced cell apoptosis. Thus, our data provide an important piece of mechanistic clues for PRRSV-induced cell apoptosis and also elucidate a novel mechanism for the 3C-like proteases in this finding.
研究领域:
病毒学
·
细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BMC Veterinary Research
·
2026
·
IF 3.1
Jing Yang,Xiaoli Zhang,Hao Wu,Wei Peng,Weiwei Su,Peibo Li
Background: Porcine reproductive and respiratory syndrome virus (PRRSV) poses a major threat to global swine production, with no clinically approved specific therapeutics. Archidendron clypearia (AC), a medicinal plant traditionally used for human upper respiratory infections, exhibits broad-spectrum antiviral activity. This study systematically evaluated the antiviral efficacy of AC against PRRSV, elucidated its pharmacodynamic material basis through comprehensive chemical profiling, and explored the targeted molecular mechanisms of its core active component, 7-GTDF. Results: Screening of 30 herbal ethanol extracts based on a PRRSV-EGFP fluorescence phenotype identified AC as possessing significant anti-PRRSV activity. In Marc-145 cells and porcine alveolar macrophages (PAMs), AC inhibited the replication of PRRSV-Li11 and PRRSV-CHR6 at both the mRNA and protein levels. Time-of-addition assays indicated that AC acts by inactivating the virus and interfering with early infection stages. Phytochemical analysis identified 40 constituents in AC, with 7-O-galloyltricetiflavan (7-GTDF) quantified via high-performance liquid chromatography (HPLC) as the predominant compound, accounting for 37.59% of the total peak area. Network pharmacology combined with experimental validation demonstrated that AC suppresses the PRRSV-induced overexpression of TNF-α, IL-1β, and IL-6 in PAMs by modulating the TLR4/NF-κB signaling pathway. Subsequent screening of the primary compounds in AC revealed that 7-GTDF exhibits significant anti-PRRSV activity. Molecular docking and molecular dynamics simulations indicated a stable interaction between 7-GTDF and the host CD163 receptor. Finally, cellular thermal shift assay (CETSA) confirmed this target engagement, demonstrating that 7-GTDF binds to the CD163 receptor and reduces its thermal stability. Conclusions: These data indicate that AC and its constituent 7-GTDF inhibit PRRSV infection through mechanisms involving CD163 targeting and inflammatory pathway modulation. These findings provide a pharmacological basis for evaluating AC as a potential antiviral candidate in swine health management.
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DOI
PubMed
高影响因子
ANTIVIRAL RESEARCH
·
2024
·
IF 4.5
Zhanding Cui,Jing Zhang,Jinlong Wang,Jinlong Liu,Pu Sun,Jiaoyang Li,Guoxiu Li,Ying Sun,Juanbin Ying,Kun Li,Zhixun Zhao,Hong Yuan,Xingwen Bai,Xueqing Ma,Pinghua Li,Yuanfang Fu,Huifang Bao,Dong Li,Qiang Zhang,Zaixin Liu,Yimei Cao,Zengjun Lu
Porcine Reproductive and Respiratory Syndrome (PRRS) presents a formidable viral challenge in swine husbandry. Confronting the constraints of existing veterinary pharmaceuticals and vaccines, this investigation centers on Caffeic Acid Phenethyl Ester (CAPE) as a prospective clinical suppressant for the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV). The study adopts an integrated methodology to evaluate CAPE's antiviral attributes. This encompasses a dual-phase analysis of CAPE's interaction with PRRSV, both in vitro and in vivo , and an examination of its influence on viral replication. Varied dosages of CAPE were subjected to empirical testing in animal models to quantify its efficacy in combating PRRSV infections . The findings reveal a pronounced antiviral potency, notably in prophylactic scenarios. As a predominant component of propolis, CAPE stands out as a promising candidate for clinical suppression, showing exceptional effectiveness in pre-exposure prophylaxis regimes. This highlights the potential of CAPE in spearheading cutting-edge strategies for the management of future PRRSV outbreaks.
研究领域:
兽医学
·
病毒学
·
药理学
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DOI
PubMed
高影响因子
Autophagy
·
2023
·
IF 13.3
Jia Li,Yanrong Zhou,Wenkai Zhao,Jiao Liu,Rizwan Ullah,Puxian Fang,Liurong Fang,Shaobo Xiao
Porcine reproductive and respiratory syndrome virus (PRRSV) is a typical immunosuppressive virus devastating the global swine industry. DEAD-box helicases (DDXs) are a family of ATP-dependent RNA helicases that are predominantly implicated in modulating cellular RNA metabolism. Meanwhile, a growing number of studies have suggested that some DDXs are associated with innate immunity and virus infection, so they are considered potential antiviral targets. Herein, we screened 40 DDXs and found that ectopic expression of DDX10 exhibited a significant anti-PRRSV effect, while DDX10 knockdown promoted PRRSV proliferation. Further analysis revealed that DDX10 positively regulates type I interferon production, which may contribute to its anti-PRRSV effect. Interestingly, PRRSV infection promoted DDX10 translocation from the nucleus to the cytoplasm for macroautophagic/autophagic degradation to block the antiviral effect of DDX10. By screening PRRSV-encoded proteins, we found that the viral envelope (E) protein interacted with DDX10. In line with the autophagic degradation of DDX10 during PRRSV infection, E protein could induce autophagy and reduce DDX10 expression in wild-type cells, but not in ATG5 or ATG7 knockout (KO) cells. When further screening the cargo receptors for autophagic degradation, we found that SQSTM1/p62 (sequestosome 1) interacted with both DDX10 and E protein, and E protein-mediated DDX10 degradation was almost entirely blocked in SQSTM1 KO cells, demonstrating that E protein degrades DDX10 by promoting SQSTM1-mediated selective autophagy. Our study reveals a novel mechanism by which PRRSV escapes host antiviral innate immunity through selective autophagy, providing a new target for developing anti-PRRSV drugs.Abbreviations: ACTB: actin beta; ATG: autophagy related; co-IP: co-immunoprecipitation; CQ: chloroquine; DDX10: DEAD-box helicase 10; E: envelope; EGFP: enhanced green fluorescent protein; hpi: hours post infection; hpt: hours post transfection; IFA: indirect immunofluorescence assay; IFN-I: type I IFN; IFNB/IFN-β: interferon beta; IRF3: interferon regulatory factor 3; ISGs: interferon-stimulated genes; KO: knockout; MAP1LC3B/LC3: microtubule associated protein 1 light chain 3 beta; mAb: monoclonal antibody; MOI: multiplicity of infection; NBR1: NBR1 autophagy cargo receptor; NFKB/NF-κB: nuclear factor kappa B; OPTN: optineurin; ORF: open reading frame; PRRSV: porcine reproductive and respiratory syndrome virus; SeV: sendai virus; siRNA: small interfering RNA; SQSTM1/p62: sequestosome 1; TCID50: 50% tissue culture infective dose; WT: wild type.
研究领域:
病毒学
·
免疫学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
VETERINARY MICROBIOLOGY
·
2023
·
IF 3.3
Lujie Zhang,Xing Liu,Jian Mao,Yangyang Sun,Yanni Gao,Juan Bai,Ping Jiang
Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important causative agents in the pig industry worldwide, causing reproductive failure in sows and respiratory problems in growing pigs. Glucose metabolism is a major pathway for energy production and interacts with many cellular processes, such as innate immunity response. It is unclear whether PRRSV infection can use the glucose metabolic pathway to generate immune escape in favor of viral replication. Here, we found that high glucose promotes PRRSV replication and glycolysis, and inhibits poly(I:C)-induced RLR signaling. Conversely, inhibition of the glycolysis pathway significantly promoted poly(I:C)-induced RLR signaling and inhibited PRRSV replication, suggesting that glycolysis promotes PRRSV replication by inhibiting interferon signaling. Furthermore, PRRSV promotes glycolysis to produce lactate, which acts as a key metabolite to promote viral replication by inhibiting RLR signaling by targeting MAVS. And the glycolytic inhibitors targeting HK2 and LDHA in glycolysis could inhibit PRRSV replication. Taken together, these findings suggested that PRRSV infection promotes glycolysis to produce lactate, which targets MAVS to inhibit RLR signaling and thus promote viral replication. Our findings provide an insight into the pathogenesis of PRRSV and offer a theoretical basis for further development of antiviral therapeutic targets.
研究领域:
病毒学
·
免疫学
·
分子生物学
·
细胞代谢
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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）