Cell Reports Medicine
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2025
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IF 10.6
Zhi Yang,Yizheng Yao,Xi Chen,Victoria Madigan,Shanrui Pu,Xianqun Fan,Jun Pu,Fengfeng Bei
Efficient gene delivery vectors are crucial for respiratory and lung disease therapies. We report that AAV.CPP.16, an engineered adeno-associated virus (AAV) variant derived from AAV9, efficiently transduces airway and lung cells in mice and non-human primates via intranasal administration. AAV.CPP.16 outperforms AAV6 and AAV9, two wild-type AAVs with demonstrated tropism for respiratory tissues, and efficiently targets key respiratory cell types. It supports gene supplementation and editing therapies in two clinically relevant mouse models of respiratory and lung diseases. A single intranasal dose of AAV.CPP.16 expressing a dual-target, vascular endothelial growth factor (VEGF)/transforming growth factor (TGF)-β1-neutralizing protein protected lungs from idiopathic pulmonary fibrosis, while a similar application of AAV.CPP.16 carrying an “all-in-one” CRISPR-Cas13d system inhibited transcription of the SARS-CoV-2-derived RNA-dependent RNA polymerase (Rdrp) gene. Our findings highlight AAV.CPP.16 as a promising vector for respiratory and lung gene therapy.
研究领域:
医学
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基因治疗
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病毒学
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DOI
PubMed
高影响因子
Computational and Structural Biotechnology Journal
·
2023
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IF 6
Boyu Pan,Senbiao Fang,Liangjiao Wang,Zhanyu Pan,Min Li,Liren Liu
The emergence of SARS-CoV-2-Spike mutants not only enhances viral infectivity but also lead to treatment failure. Gaining a comprehensive understanding of the molecular binding mode between the mutant SARS-CoV-2-Spike and human ACE2 receptor is crucial for therapeutic development against this virus. Building upon our previous predictions and verifications regarding heightened viral infectivity of six potential SARS-CoV-2-Spike mutants, this study aims to further investigate the potential disruption of the interaction between these mutants and ACE2 by quercetin, a Chinese herbal compound. Molecular docking and dynamics simulations results reveal that the binding sites of quercetin particularly enriched around a specific “cavity” at the interface of Spike/ACE2 complex, indicating a favorable region for quercetin to interfere with Spike/ACE2 interaction. Virus infection assay confirms that quercetin not only attenuates wild-type virus infectivity but also suppresses the infectivity of all six tested SARS-CoV-2-Spike mutants. Therefore, quercetin represents a promising therapeutic candidate against both wild-type and potential future variants of SARS-CoV-2 exhibiting high viral infectivity.
研究领域:
病毒学
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药理学
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计算生物学
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DOI
PubMed
高影响因子
INSECT MOLECULAR BIOLOGY
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2024
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IF 2.3
Hui-Hua Cao,Wei-Wei Kong,Xi-Ya Chen,Sadaf Ayaz,Cai-Ping Hou,Yi-Sheng Wang,Shi-Huo Liu,Jia-ping Xu
The RNA interference pathway mediated by microRNAs (miRNAs) is one of the methods to defend against viruses in insects. Recent studies showed that miRNAs participate in viral infection by binding to target genes to regulate their expression. Here, we found that the Bombyx mori miRNA, miR-6498-5p was down-regulated, whereas its predicted target gene pyridoxal phosphate phosphatase PHOSPHO2 ( BmPLPP2 ) was up-regulated upon Bombyx mori nucleopolyhedrovirus (BmNPV) infection. Both in vivo and in vitro experiments showed that miR-6498-5p targets BmPLPP2 and suppresses its expression. Furthermore, we found miR-6498-5p inhibits BmNPV genomic DNA (gDNA) replication, whereas BmPLPP2 promotes BmNPV gDNA replication. As a pyridoxal phosphate (PLP) phosphatase (PLPP), the overexpression of BmPLPP2 results in a reduction of PLP content, whereas the knockdown of BmPLPP2 leads to an increase in PLP content. In addition, exogenous PLP suppresses the replication of BmNPV gDNA; in contrast, the PLP inhibitor 4-deoxypyridoxine facilitates BmNPV gDNA replication. Taken together, we concluded that miR-6498-5p has a potential anti-BmNPV role by down-regulating BmPLPP2 to modulate PLP content, but BmNPV induces miR-6498-5p down-regulation to promote its proliferation. Our findings provide valuable insights into the role of host miRNA in B. mori –BmNPV interaction. Furthermore, the identification of the antiviral molecule PLP offers a novel perspective on strategies for preventing and managing viral infection in sericulture.
研究领域:
分子生物学
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病毒学
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昆虫学
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RNA干扰
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DOI
PubMed
高影响因子
CELLULAR SIGNALLING
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2025
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IF 3.7
Jie Liu,Mei-qi He,Gao-peng Guan,Xin-xing Wan,Ping Jin
Type 1 diabetes (T1D) is an autoimmune disease characterized by hyperglycemia caused by the destruction of insulin-producing β cells. Viral infection is an important environmental factor which is associated with the islet autoimmunity in genetically susceptible individuals. Loss of β-cells and triggering of insulitis following viral infection could result from several non-exclusive mechanisms. Despite a significant increase in ISG15 levels following viral infection, the specific role of ISG15 in the impairment of insulin-producing β-cells is unclear. To address this issue at the clinical level, we conducted this experimental work, and found elevated levels of ISG15 in the peripheral blood of T1D patients, suggesting a potential link between ISG15 and T1D. In the T1D animal model, we discovered that both ISG15 levels and cellular apoptosis were increased in pancreatic islet tissue. To investigate at the cellular level, we cultured MIN6 cells in the presence of supernatants derived from iBMDM cells transfected with poly(I:C) (PIC), a viral mimic. This exposure led to an upregulation of ISG15 expression in MIN6 cells, which was accompanied by the suppression of their functional capabilities and viability. Intriguingly, the direct transfection of MIN6 cells with PIC increased the expression of ISG15. We further found that elevated levels of ISG15 had a direct inhibitory effect on insulin secretion and it also contributed to β-cell apoptosis in a TNF-α-dependent manner. In conclusion, our study revealed a potential underlying mechanism through which ISG15 increases the apoptosis of β-cells, providing valuable insights that could facilitate the development of T1D treatment strategies.
研究领域:
免疫学
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内分泌学
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糖尿病学
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DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
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2022
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IF 8.008
Xueping Yang,Jingyun Li,Suixin Zhang,Chao Li,Jiehua Ma
CRISPR/Cas-based systems are highly attractive for developing next-generation diagnostic technologies because of their intrinsic merits such as simplicity, sensitivity, and specificity. However, currently, nucleic acid amplification procedures are still needed to achieve attomolar sensitivity in most CRISPR/Cas-based assays, which causes high cost, operation difficulty, and low efficiency. Herein, we combine the CRISPR/Cas12a-based assay and a single-microbead detection platform for one-step and amplification-free detection of DNA at the single-molecule level. By modifying DNA reporters on a biomimetic membrane-coated microbead, the activated Cas12a by targets will cleave these reporters and lighten the bead within 10 min. The method allows the detection of the target down to three copies in a 5 μL sample. Furthermore, we successfully apply this method for the specific identification of viral infection, foodborne bacteria, and DNA mutation in real samples without extra nucleic acid amplification. We believe that this approach offers new insights for developing CRISPR/Cas-based DNA assays in biomedical applications.
研究领域:
分子生物学
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生物技术
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诊断技术
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DOI
PubMed
高影响因子
Nature Protocols
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2022
·Vol. 18
·期 2
·458-489
·
IF 17.021
Liu Hao-Yang,Wang Zhi-Gang,Liu Shu-Lin,Pang Dai-Wen
Single-virus tracking (SVT) offers the opportunity to monitor the journey of individual viruses in real time and to explore the interactions between viral and cellular structures in live cells, which can assist in characterizing the complex infection process and revealing the associated dynamic mechanisms. However, the low brightness and poor photostability of conventional fluorescent tags (e.g., organic dyes and fluorescent proteins) greatly limit the development of the SVT technique, and challenges remain in performing multicolor SVT over long periods of time. Owing to the outstanding photostability, high brightness and narrow emission with tunable color range of quantum dots (QDs), QD-based SVT (QSVT) enables us to follow the fate of individual viruses interacting with different cellular structures at the single-virus level for milliseconds to hours, providing more accurate and detailed information regarding viral infection in live cells. So far, the QSVT technique has yielded spectacular achievements in uncovering the mechanisms associated with virus entry, trafficking and egress. Here, we provide a detailed protocol for QSVT implementation using the viruses that we have previously studied systematically as an example. The specific procedures for performing QSVT experiments in live cells are described, including virus preparation, the QD labeling strategies, imaging approaches, image processing and data analysis. The protocol takes 1–2 weeks from the preparation of viruses and cellular specimens to image acquisition, and 1 d for image processing and data analysis.
研究领域:
病毒学
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细胞生物学
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成像技术
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分子生物学
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
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IF 19
Shunyu Xiang,Jing Wang,Yang Shen,Xingyi Luo,Xiaoyan Wang,Changyun Liu,Xinyu Chen,Hüseyin Enis Karahan,Jin Huang,Alberto Bianco,Xianchao Sun
Manganese is vital for plant growth and disease resistance but remains underutilized as a bioactive agent due to its toxicity at high concentrations. Here, an effective antiviral nanopesticide system utilizing Mn ions (Mn 2+ ) within safe limits is described. Briefly, cellulose nanocrystals (CNCs) are employed as bio-sourced carrier surfaces and polydopamine (PDA) as a stabilizing and chelating agent for Mn 2+ . By impregnating Mn 2+ onto PDA-coated CNCs, the stable CNC@PDA@Mn 2+ (CPM) composite is fabricated. The CPM composite exhibits a substantially strengthened inhibitory effect on virus infectivity and curtails virus accumulation in Nicotiana benthamiana . The synergistic effects of CPM stem from its ability to directly disrupt viral particles and activate the plant-immunity-related antioxidant systems. Additionally, H 2 O 2 generated by the CPM-activated superoxide dismutase potentially serves as a molecular signal to overexpress the disease-resistance gene harpin-induced 1 ( NbHin1 ) by sulfinylating CCA1 Hiking Expedition and enhance its binding to NbHin1 promoter. Subsequently, this upregulation coordinates the activation of NbHin1 -dependent macroautophagy, triggering multiple antiviral defense mechanisms. Thus, this design achieves highly potent broad-spectrum antiviral activity at low concentrations of manganese (16 µg mL −1 ). Notably, this work pioneers the use of Mn 2+ in triggering plant antiviral defense, offering a solid foundation for designing novel antiviral agents.
研究领域:
植物学
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植物病理学
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纳米技术
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病毒学
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生物化学
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农业科学
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产品关联
DOI
高影响因子
VETERINARY MICROBIOLOGY
·
2023
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IF 3.3
Yu Pang,Chenyu Li,Yuchen Wang,Jiao Liu,Guanning Su,Chenrui Duan,Liurong Fang,Yanrong Zhou,Shaobo Xiao
The metabolic pathways of central carbon metabolism (CCM), glycolysis and the tricarboxylic acid (TCA) cycle, are important host factors determining the outcome of viral infection . Thus, it is not surprising that viruses easily manipulate CCM for optimized replication. Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has devastated the swine industry worldwide for over 30 years. However, whether PRRSV reprograms CCM is still unclear. In this study, we found that PRRSV infection increased the intensity of cellular uptake of glucose and glutamine, two main carbon sources for mammalian cells. Deprivation of glucose and/or glutamine significantly reduced PRRSV replication; restricted entry of glucose and glutamine into CCM inhibited PRRSV proliferation. We further found that PRRSV infection elevated glycolysis and maintained the TCA cycle flux. Furthermore, preventing the flow of glycolysis or the TCA cycle led to a reduction in PRRSV proliferation. The anaplerotic usage of glutamine in the TCA cycle partially rescued PRRSV growth by replacing glutamine with α-ketoglutarate (α-KG), an intermediate of the TCA cycle. Interestingly, the addition of α-KG in replete medium also promoted PRRSV proliferation. Taken together, these results reveal that PRRSV infection promotes cellular uptake of glucose and glutamine to provide the energy and macromolecules required for PRRSV replication, and optimal PRRSV replication occurs in cells dependent on glycolysis and the TCA cycle.
研究领域:
病毒学
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代谢生物学
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动物健康
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DOI
PubMed
高影响因子
VACCINE
·
2022
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IF 4.169
Qianyu Bai,Zhiwen Wang,Yina AN,Jijing Tian,Zhilin Li,Yifei Yang,Yanjun Dong,Mingyong Chen,Tianlong Liu
Searching appropriate adjuvants for vaccine is a potent method to intense the immune efficacy. In the present study, we developed a novel Hepatitis E virus (HEV) vaccine by utilizing chitosan modified nano-graphene oxide (GO-CS) as an adjuvant to support HEV antigen P239 protein (GO/CS/P239). The characterization of GO/CS/P239 was observed by atomic force microscope. The safety of GO/CS/P239 was measured by CCK-8 method, hemolysis test and acute challenge test. The anti-HEV titers and cytokines production were analyzed by double antibody sandwich ELISA . As the results showed, by contrast with a vaccine that contained only the P239 protein, GO/CS/P239 vaccine can promote immune cells to produce more IgG antibodies and cytokines, which were able to stimulate the organism to produce stronger both cellular and humoral immunity. Collectively, GO/CS/P239 particles have been demonstrated to be safe both in vitro and in vivo, and can facilitate sufficient immune response to protect organisms from virus infection , which suggested that our exploration offers a promising alternative vaccine that can control HEV infection.
研究领域:
免疫学
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病毒学
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纳米技术
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药学
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产品关联
DOI
PubMed
高影响因子
BMC GENOMICS
·
2025
·Vol. 26
·期 1
·1-16
·
IF 3.7
Yang Xiao-Li,Wang Yang,Li Zhi,Lin Qiao-Hong,Yu Peng,Lu Meng,Li Xi-Yin,Wang Zhong-Wei,Zhang Xiao-Juan,Gui Jian-Fang,Zhou Li
Allopolyploids often exhibit enhanced resistance to pathogen stresses. However, our understanding about the patterns that allopolyploids modify homeolog expression upon pathogen invasion remains limited. Since 2012, a disease caused by herpesvirus ( Ca HV) has posed a severe threat to Carassius auratus aquaculture. Therefore, the synthesis of novel allopolyploids with enhanced resistance has become one of significant priorities for its aquaculture. In this study, we first synthesized and then established a gynogenetic Carassius alloheptaploid clone ( Ca A7n). It possesses approximately 158 chromosomes of C. gibelio and 24 haploid chromosomes of M. amblycephala . Ca HV challenge experiments showed that Ca A7n inherited high resistance from its paternal M. amblycephalus , exhibiting a 100% survival rate after Ca HV infection. Subsequently, we revealed distinct transcriptional responses among Ca A7n and its parents to Ca HV infection and identified two key modules. The egiengenes in the module that positively correlated with Ca A7n resistance were mainly enriched in chemokine activity GO terms. Finally, we described a profound expression alteration of three homeologs in Ca A7n, including additive and non-additive expression patterns. After Ca HV infection, three homeologs mainly involved in chemokine activity changed their expression patterns in Ca A7n. Moreover, homeologs derived from M. amblycephala associated with chemokine activity, which showed altered expression levels, may enhance the antiviral immune response of Ca A7n. This study not only establishes Ca A7n as a promising Ca HV-resistant candidate for aquaculture but also elucidates how allopolyploids reconfigure parental homeolog expression networks to enhance antiviral defenses, advancing our understanding of allopolyploid adaptation mechanisms under pathogenic pressure.
研究领域:
水产养殖
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免疫遗传学
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病毒学
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分子生物学
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鱼类遗传学
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比较基因组学
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产品关联
DOI
PubMed
高影响因子
Nanomedicine-Nanotechnology Biology and Medicine
·
2022
·
IF 6.458
Qiming Yin,Xiang Song,Peng Yang,Wen Yang,Xinyu Li,Xuejun Wang,Shengqi Wang
Liver injury caused by hepatitis is the pathological basis of varied hepatic diseases with high morbidity and mortality. Although siRNA appears promising in therapeutics of hepatitis, efficient and safe delivery remains a challenge. In this study, we developed a new strategy of incorporating glycyrrhizic acid (GA) and polyene phosphatidylcholine (PPC) into lipid nanoparticles (GA/PPC-modified LNPs), which was capable of promoting cellular uptake, enhancing gene-silencing, reducing cytotoxicity and improving siRNA stability. GA/PPC-modified LNP and siRNA lipoplex targeting NF-κB, a key mediator of inflammation, mitigates acute liver injury, as assessed by liver histology , hematological and pro-inflammatory cytokine analysis. Furthermore, GA/PPC-modified LNPs reveal efficiently intracellular delivery of antisense oligonucleotides (ASOs) and mRNA inhibiting viral infection. In conclusion, GA/PPC-modified LNPs could be used as a promising delivery system for nucleic acid-based therapy.
研究领域:
药理学
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分子生物学
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纳米技术
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肝病学
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2021
·
IF 6.53
Yi-yu Liang,Kun-wei Li,Feng-jv Niu,Ying Li,Hao-cheng Wei,Yun-lei Dai,Yun-yu Wang,Chang-zheng Zhou,Xin-huan Wan
Objective To investigate the antiviral effect of Salvia plebeia R. Br. polysaccharides (SPP) against RSV and underlying mechanisms. Methods SPP was extracted via alcohol-precipitation method and extract was separated into various fractions using ultrafiltration method. The polysaccharide content was determined using UV-Vis. Antiviral effect of SPP and fractions was measured using MTT method and Reed-Muench method. Sixty Balb/c mice were randomly divided into 6 groups, and received either Ribavirin or SPP. Their body weight and food intake were recorded every day throughout the experiment period. The lung index inhibition ratio and pulmonary virus titer were determined followed by the histological analysis of lungs. Furthermore, time-of-addition and effective stage analysis were carried out to determine the mechanism of action. The TLR-3 and TLR-4 levels in the lungs were determined using qRT-PCR. The levels of IFN-γ, IL-2 and TNF-α in serum were determined using ELISA. Results The SPP content is 4.396%. SPP has shown a good anti-RSV effect both in vitro (TI = 123.041) and in vivo models. The antiviral activity of fractions with molecular weight ≥ 10,000 is found to possess more potent antiviral activity than other fractions. SPP inhibits the RSV proliferation and reduces the lung lesions induced by RSV. The mechanism of action involves the inhibition of TLR-3 and TLR-4 in lungs, up-regulation of IFN-γ and IL-2, and down-regulation of TNF-α in serum. It is also shown to improve the body’s immune function. Conclusion SPP has a potential to treat diseases caused by RSV.
研究领域:
药理学
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免疫学
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病毒学
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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）