JOURNAL OF IMMUNOLOGY
·
2025
·
IF 3.4
Huang Wenji,Wang Yafang,Ji Ning,Xiao Hehe,Chen Kangyong,Guo Jiahong,Feng Jianhua,Mustafa Nageen,Wang Junya,Feng Hao,Zou Jun
A balanced IFN response, tightly regulated at multiple levels, is essential for host defense against viral infection. Tripartite motif-containing (TRIM) proteins are a large group of E3 ubiquitin ligases, and have been shown to be involved in the regulation of IFN response. However, the regulatory functions of individual TRIM proteins remain controversial. Here, we show that a virus-inducible TRIM2 homolog acts as a negative regulator for IFN production in zebrafish. Zebrafish Trim2a was upregulated in response to spring viremia of carp virus (SVCV) infection, and knockout of Trim2a significantly increased the expression of antiviral genes, leading to enhanced resistance to SVCV. Overexpression of Trim2a resulted in pronounced ubiquitination of IFN regulatory factor 3 (IRF3) via K11, K27, K29, and K48, promoting IRF3 degradation and stability of SVCV phosphoprotein to favor viral replication. Moreover, TRIM2a induced ubiquitination of autophagic cargo receptor p62, which then interacted with IRF3, instigating IRF3 degradation. Further, the inhibitory effects of TRIM2a on IFN production were also observed in human HEK293 cells, suggesting that the regulatory functions of TRIM2 are likely to be conserved during evolution. Collectively, our findings demonstrate that TRIM2a is a negative regulator of IFN production, and could serve as a potential target to dampen exacerbated IFN response triggered by aberrant activation of retinoic acid-inducible gene 1 (RIG-I)-like receptors. Our study provides insights into a previously uncharacterized role of TRIM2 in the regulation of IFN signaling.
研究领域:
免疫学
·
病毒学
·
分子生物学
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DOI
PubMed
高影响因子
ANTIVIRAL RESEARCH
·
2015
·
IF 3.938
Shaoyang Zhang,Limei Zhong,Bing Chen,Ting Pan,Xue Zhang,Liting Liang,Qianwen Li,Ziying Zhang,Hui Chen,Jie Zhou,Haihua Luo,Hui Zhang,Chuan Bai
HIV-1 Vif protein is one of the most crucial accessory proteins for viral replication. It efficiently counteracts the important host restriction factor APOBEC3G (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G, A3G) which is lethal to HIV-1 by causing G to A mutation of viral genome. Vif protein mediates degradation of APOBEC3G via the complicated protein–protein interactions of Vif, APOBEC3G, Elongin C/B and Cullin 5. The importance of Vif–APOBEC3G complex makes it a good potential target to develop new therapeutics of HIV-1. We identified a potent HIV-1 replication inhibitor (ZBMA-1, IC 50 = 1.01 μM) that efficiently protected APOBEC3G protein by targeting Vif–APOBEC3G complex. The co-immunoprecipitation and docking studies indicated that compound ZBMA-1 affected the binding of Elongin C with Vif protein.
研究领域:
病毒学
·
分子生物学
·
药物开发
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DOI
PubMed
高影响因子
JOURNAL OF MEDICAL VIROLOGY
·
2022
·Vol. 94
·期 6
·2519-2527
·
IF 20.693
Lu Lv,Haoran Cui,Zhiyang Chen,Yixuan Zhou,Leiliang Zhang
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus affecting human health globally. G-quadruplex secondary structures attract great attention as potential targets for antiviral strategy. In this study, we show that the CHIKV genome possesses several conserved potential G-quadruplex sequences. G-quadruplex ligands BRACO-19 and TMPyP4 could stabilize the CHIKV G-quadruplex and inhibit the transcription of constructs containing CHIKV G-quadruplex sequences. Importantly, BRACO-19 and TMPyP4 suppress CHIKV replication. Our study not only reinforces the presence of viral G-quadruplex sequences but also suggests that targeting G-quadruplex structure could represent a novel strategy to inhibit CHIKV. Highlights CHIKV possesses conserved G-quadruplexes G-quadruplex ligands stabilize CHIKV G-quadruplexes with high affinities G-quadruplex structures reduce the transcription of the GFP reporter gene containing CHIKV G-quadruplex G-quadruplex ligands BRACO-19 and TMPyP4 inhibit CHIKV replication
研究领域:
病毒学
·
分子生物学
·
药物化学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2022
·
IF 8.786
Xin Zhao,Wenji Huang,Yanjie Shi,Jiahong Guo,Hehe Xiao,Ning Ji,Jianhua Feng,Huifeng Dang,Jun Zou
PLAAT1 is a member of the PLAAT protein family and plays important roles in tumor suppression, transglutaminase activation and peroxisomal biogenesis. Recently, PLAAT1 has been shown to promote degradation of p53 protein and cellular organelles such as mitochondria, endoplasmic reticulum and lysosome. In this study, we show that PLAAT1 inhibits the production of type I interferon and promotes virus replication in zebrafish. Overexpression of Plaat1 in zebrafish cells suppresses antiviral responses and promotes virus replication. Mechanistically, PLAAT1 interacts with IRF3 and IRF7 to initiate degradation of IRF3 and IRF7, which can be attenuated by 3-methyladenine, an inhibitor of autophagosome. Our study provides novel insights into the functions of PLAAT1 in host immune response to viral infection.
研究领域:
免疫学
·
病毒学
·
分子生物学
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DOI
PubMed
高影响因子
VIROLOGY
·
2024
·
IF 2.8
Ping Yang,Zheng-Jian Wang,Hai-Tao Lu,Xu-Meng Feng,Jing-Long Ye,Guangchuan Wang,Cheng-Feng Qin,Qing Ye,Zhong-Yu Liu
The knowledge on the life cycle of flaviviruses is still incomplete, and no direct-acting antivirals against their infections are clinically available. Herein, by screening via a Zika virus (ZIKV) replicon assay, we found that the N-terminus of NS2A exhibited great tolerance to the insertions of different split fluorescent proteins (split-FPs). Furthermore, both ZIKV and dengue virus encoding a split-FP-tagged NS2A propagated efficiently, and the split-FP-tagged ZIKVs had good genetic stability. Robust green fluorescence was observed in the reporter cell lines infected with these viruses and the fluorescence responded to anti-flavivirus chemicals with high specificity and sensitivity. Moreover, the sites of viral RNA replication were illuminated in live cells. Interestingly, by blocking viral RNA synthesis with an NS5 inhibitor, we found a correlation between the morphological characteristics of potential replication organelles and RNA amplification, highlighting that the NS2A-tagged viruses are of great value for the in-depth understanding of flavivirus replication mechanisms.
研究领域:
病毒学
·
分子生物学
·
药物研发
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产品关联
DOI
PubMed
高影响因子
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
·
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
·
病毒学
·
免疫学
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产品关联
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
PROTEIN EXPRESSION AND PURIFICATION
·
2022
·
IF 2.025
Yi Rong,Chaofeng Zhang,Wen-Chao Gao,Cheng Zhao
The main protease (M pro ) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a vital role in viral replication. To study the function of M pro and screen inhibitors targeting M pro , it is necessary to prepare high-purity and high-activity M pro . In this study, four types of SARS-CoV-2 M pro s containing different termini were prepared, and their activities were determined successfully. The results showed that the activity of wild-type (WT) M pro was the highest, and the additional residues at the N-terminus but not at the C-terminus had a major effect on the enzyme activity. To explain this, the alignment of structures of different forms of M pro was determined, and the additional residues at the N-terminus were found to interfere with the formation of the substrate binding pocket. This study confirms the importance of the natural N-terminus to the activity of M pro and suggests that WT-GPH 6 (M pro with eight additional residues at the C-terminus) can be used as a substitute for authentic M pro to screen inhibitors. In short, this study provides a reference for the expression and purification of new coronaviruses confronted in the future.
研究领域:
病毒学
·
生物化学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
VETERINARY MICROBIOLOGY
·
2024
·
IF 2.4
Guangbin Bao,Shinuo Fan,Chunyan Hu,Chen Li,Fei Ma,Guijun Wang,Hongjie Fan,Qing Wang
Duck Tembusu virus (DTMUV) is a newly emerging pathogen that causes massive economic losses to the poultry industry in China and neighbouring countries. Vimentin, an intermediate filament protein, has been demonstrated to be involved in viral replication during infection. However, the specific role of vimentin in DTMUV replication has not been determined. In this study, we found that overexpression of vimentin in BHK-21 cells can inhibit DTMUV replication. Moreover, DTMUV replication was enhanced after vimentin expression was reduced in BHK-21 cells via small interfering RNA (siRNA). Further research indicated that DTMUV infection had no effect on the transcription or expression of vimentin. However, we found that DTMUV infection induced vimentin rearrangement, and the rearrangement of vimentin was subsequently confirmed to negatively modulate viral replication through the use of a vimentin network disrupting agent. Vimentin rearrangement is closely associated with its phosphorylation. Our experiments revealed that the phosphorylation of vimentin at Ser56 was promoted in the early stage of DTMUV infection. In addition, by inhibiting the phosphorylation of vimentin at Ser56 with a CDK5 inhibitor, vimentin rearrangement was suppressed, and DTMUV replication was significantly enhanced. These results indicated that DTMUV infection induced vimentin phosphorylation and rearrangement through CDK5, resulting in the inhibition of DTMUV replication. In summary, our study reveals a role for vimentin as a negative factor in the process of DTMUV replication, which helps to elucidate the function of cellular proteins in regulating DTMUV replication.
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
Microbiology Spectrum
·
2023
·Vol. 11
·期 3
·
IF 3.7
Jinchao Xing,Chen Hu,Siqi Che,Yixin Lan,Lihong Huang,Lele Liu,Youqin Yin,Huanan Li,Ming Liao,Wenbao Qi
Japanese encephalitis virus (JEV) is a typical mosquito-borne flavivirus that can cause central nervous system diseases in humans and animals. Host factors attempt to limit virus replication when the viruses invade the host by using various strategies for replication. It is essential to clarify the host factors that affect the life cycle of JEV and explore its underlying mechanism. Here, we found that USP1-associated factor 1 (UAF1; also known as WD repeat-containing protein 48) modulated JEV replication. We found that JEV propagation significantly increased in UAF1-depleted Huh7 cells. Moreover, we found that knockdown of UAF1 activated cell autophagic flux in further functional analysis. Subsequently, we demonstrated that autophagy can be induced by JEV, which promotes viral replication by inhibiting interferon-stimulated gene (ISG) expression in Huh7 cells. The knockdown of UAF1 reduced ISG expression during JEV infection. To explore the possible roles of autophagy in UAF1-mediated inhibition of JEV propagation, we knocked out ATG7 to generate autophagy-deficient cells and found that depletion of UAF1 failed to promote JEV replication in ATG7 knockout cells. Moreover, in ATG7-deficient Huh7 cells, interference with UAF1 expression did not lead to the induction of autophagy. Taken together, these findings indicate that UAF1 is a critical regulator of autophagy and reveal a mechanism by which UAF1 knockdown activates autophagy to promote JEV replication.IMPORTANCE Host factors play an essential role in virus replication and pathogenesis. Although UAF1 is well known to form complexes with ubiquitin-specific proteases, little is known about the function of the UAF1 protein itself. In this study, we confirmed that UAF1 is involved in JEV replication. Notably, we discovered a novel function for UAF1 in regulating autophagy. Furthermore, we demonstrated that UAF1 modulated JEV replication through its autophagy regulation. This study is the first description of the novel function of UAF1 in regulating autophagy, and it clarifies the underlying mechanism of the antiviral effect of UAF1 against JEV. These results provide a new mechanistic insight into the functional annotation of UAF1 and provide a potential target for increasing virus production during vaccine production.
研究领域:
病毒学
·
分子生物学
·
细胞生物学
·
传染病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 23
·
IF 4.9
Huiqiang Wang,Ya Wang,Shuo Wu,Lijun Qiao,Wen Sheng,Haiyan Yan,Kun Wang,Ge Yang,Jiandong Jiang,Yuhuan Li
Previous studies have reported that Enterovirus A71 (EV-A71) infection could activate STING-related signaling pathways in vitro, but the role of STING in EV-A71 infection in vivo and the associated immune regulatory mechanisms remain unclear. Here, we used the STING-specific agonist diABZI to activate STING and STING-knockout mice to jointly study the role and mechanism of regulating STING on EV-A71 infection in vivo. The results showed that activating STING could inhibit the in vivo replication of EV-A71, alleviate clinical symptoms in infected mice, and increase the survival rate. Conversely, STING knockout significantly promoted viral replication in vivo and increased the lethality and severity of EV-A71 infection. Mechanistic studies further revealed that STING activation exerts its antiviral effects by stimulating interferon signaling pathways, upregulating the expression of interferon-stimulated genes (ISGs). Additionally, STING activation also modulated the serum cytokine response profile. Moreover, STING activation drove the expansion of diverse immune cell populations, including T cells, natural killer (NK) cells and myeloid cells. In contrast, STING knockout not only reduced the proportion of thymic T cells and impeded T cell developmental progression from double-positive (DP) to single-positive (SP) stages, but also impaired the effector functions of CD8+ T cells and NK cells during viral infection. In summary, this study demonstrates that STING activation effectively suppresses EV-A71 replication and mitigates infection symptoms by modulating immune and inflammatory responses. These findings provide a foundational framework for understanding how STING coordinates antiviral immunity and inform future investigations into STING-targeted therapies for viral infections.
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产品关联
DOI
PubMed
高影响因子
VETERINARY MICROBIOLOGY
·
2025
·
IF 2.7
Xiaomei Du,Qi Xiao,Li Yang,Yiyi Shan,Yueqing Hu,Wenbin Bao,Shenglong Wu,Zhengchang Wu
Porcine circovirus type 2 (PCV2) is the main pathogen causing postweaning multisystemic wasting syndrome, which leads to enormous losses for porcine industry. However, the regulatory mechanism of PCV2 replication in host cells remains not been clarified. Here, pig DNMT3B was identified as be a host regulator associated with PCV2 infection via RNA-seq analysis. We demonstrated that upregulation of DNMT3B expression can effectively inhibit PCV2 replication in PK15 cells. Besides, TMEM37 acts as a key downstream target of DNMT3B in PCV2-infected PK15 cells. TMEM37 knockdown significantly slowed Ca 2+ influx, and thus inhibited PCV2 replication. Taken together, DNMT3B is required for the PCV2-based infection regulation in host cells. Our findings indicated that DNMT3B inhibits PCV2 replication via targeting TMEM37 to regulate Ca 2+ influx in PK15 cells, which offering a theoretical foundation for the use of this gene as a key biomarker for breeding strategies seeking to improve porcine disease resistance.
研究领域:
兽医学
·
分子生物学
·
病毒学
·
动物遗传学
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产品关联
DOI
PubMed
高影响因子
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