Communications Biology
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2023
·Vol. 6
·期 1
·1-12
·
IF 5.9
Wang You-Yuan,Zhen Cheng,Hu Wei,Huang Hui-Huang,Li Yan-Jun,Zhou Ming-Ju,Li Jing,Fu Yu-Long,Zhang Peng,Li Xiao-Yu,Yang Tao,Song Jin-Wen,Fan Xing,Zou Jun,Meng Si-Run,Qin Ya-Qin,Jiao Yan-Mei,Xu Ruonan,Zhang Ji-Yuan,Zhou Chun-Bao,Yuan Jin-Hong,Huang Lei,Shi Ming,Cheng Liang,Wang Fu-Sheng,Zhang Chao
CD8 + T cells are essential for long-lasting HIV-1 control and have been harnessed to develop therapeutic and preventive approaches for people living with HIV-1 (PLWH). HIV-1 infection induces marked metabolic alterations. However, it is unclear whether these changes affect the anti-HIV function of CD8 + T cells. Here, we show that PLWH exhibit higher levels of plasma glutamate than healthy controls. In PLWH, glutamate levels positively correlate with HIV-1 reservoir and negatively correlate with the anti-HIV function of CD8 + T cells. Single-cell metabolic modeling reveals glutamate metabolism is surprisingly robust in virtual memory CD8 + T cells (TVM). We further confirmed that glutamate inhibits TVM cells function via the mTORC1 pathway in vitro. Our findings reveal an association between metabolic plasticity and CD8 + T cell-mediated HIV control, suggesting that glutamate metabolism can be exploited as a therapeutic target for the reversion of anti-HIV CD8 + T cell function in PLWH.
研究领域:
免疫学
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病毒学
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代谢学
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HIV/AIDS研究
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PubMed
高影响因子
BME Frontiers
·
2025
·
IF 7.7
Yirui Zhang,Jieyu Yan,Wangheng Hou,Qian Gao,Tao Zhang,Yan Gao,Jingwen Li,Kun Han
Objective: Accurate and rapid detection of disease biomarkers is critical for early diagnosis, timely intervention, and effective disease management. Impact Statement: This strategy is exemplified through the development of 2 biosensors for detecting HIV-1 DNA and HIV-1 p24, biomarkers associated with acquired immunodeficiency syndrome (AIDS). Introduction: We propose a general biosensing strategy that leverages a treble signal amplification cascade, demonstrating its versatility and applicability across diverse biomolecular targets. Methods: The method integrates multiple amplification mechanisms to achieve unparalleled sensitivity. Initially, the hybridization of 2 aided probes with the target triggers isothermal amplification facilitated by polymerase and nicking enzyme, providing a robust preliminary signal enhancement. Repeated cycles of primer extension, nicking, and signal primer dissociation then generate multiple signal primers. These primers are further amplified via rolling circle amplification (RCA), resulting in an important secondary signal boost. Finally, the amplified products activate CRISPR-Cas12a-mediated trans-cleavage, achieving a tertiary level of signal enhancement. Results: This cascade amplification approach achieves remarkable sensitivity, with detection limits of 62 aM for nucleic acids and 8.48 pg/ml for proteins, positioning it as a broadly applicable framework. Clinical samples were assayed, which indicates its capability in clinical diagnosis. Conclusion: Beyond HIV detection, the modular design of this strategy allows adaptation for various biomarkers, showcasing its potential as a universal platform for molecular diagnostics in healthcare and research.
研究领域:
生物传感器
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分子诊断
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病毒学
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临床诊断
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生物医学工程
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核酸扩增
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蛋白质检测
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PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2013
·
IF 5.437
Wenjiao Zhou,Xue Gong,Yun Xiang,Ruo Yuan,Yaqin Chai
Visual detections have attracted great research attentions recently due to their convenient monitoring of the target analytes without using any advanced instruments. However, achieving visual detection of trace amounts of biomolecules with PCR-like sensitivity remains a major challenge. In current work, we describe a new quadratic signal amplification strategy for sensitive visual detection of HIV DNA biomarkers based on exonuclease III (Exo III)-assisted DNA recycling amplification and DNAzymes. The presence of the target HIV DNA leads to two independent and simultaneous DNA recycling processes to achieve quadratic signal amplification with the assistance of Exo III. This quadratic signal amplification results in catalytic cleavage of the G-quadruplex sequence-locked hairpin probes to release numerous active G-quadruplex sequences, which further associate with hemin to form DNAzymes and cause significantly intensified color change for sensitive and visual detection of HIV DNA down to 2.5 pM. The proposed visual detection method employs un-modified hairpin DNA as probes, avoids using any complex and expensive instruments for signal transduction and is essentially simple. This method also shows single-base mismatch discrimination capability as well. All these features make our developed DNA detection method holds great potential for visual monitoring of various DNA biomarkers at ultralow levels with careful and proper probe designs.
研究领域:
分子生物学
·
分析化学
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DOI
PubMed
高影响因子
JOURNAL OF LEUKOCYTE BIOLOGY
·
2025
·
IF 3.1
Song Zichen,Wang Jiangrong,Zheng Zhihang,He Zhixiang,Xun Jingna,Gu Ling,Shen Yinzhong,Chen Jun
Inhibiting the metabolic activity of CD4+ T cells can effectively reduce HIV infection. Mitochondria, as critical organelles in eukaryotic metabolism, play a significant role in the progression of many diseases. The change of mitochondrial dynamics is an important process of mitochondrial regulation of cell metabolic activity. However, it remains uncertain whether regulating mitochondrial dynamics is a viable approach to reducing HIV infection. In this study, we demonstrated that promoting mitochondrial fusion in Jurkat cells through treatment with the mitochondrial fusion promoter M1 and the dynamin-related protein 1 (Drp1) inhibitor Mdivi1 conferred resistance to single-round VSVG-HIVNL4-3-GFP viral infection. Targeted metabolomics analysis revealed and subsequently confirmed the potential involvement of citrate in reducing HIV infection, which has been subsequently verified. And we found that plasma citrate level was negatively associated with HIV disease progression. Multi-omics results showed that citric acid leads to a decrease in the level of nucleotide metabolism in Jurkat cells. In conclusion, increased citrate levels resulting from mitochondrial fusion significantly impair the ability of HIV to infect cells, which may due to regulate nucleotide metabolism
研究领域:
免疫学
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病毒学
·
代谢组学
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DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
·
2013
·
IF 3.848
Wu Lian,Mingyi Wu,Ning Huang,Na Gao,Chuang Xiao,Zi Li,Zhigang Zhang,Yongtang Zheng,Wenlie Peng,Jinhua Zhao
Background Fucosylated glycosaminoglycan (FG) is a novel glycosaminoglycan with a chondroitin sulfate-like backbone and fucose sulfate branches. The aim of this study is to investigate the mechanism and structure–activity relationships (SAR) of FG for combating HIV-1 infection. Methods Anti-HIV activities of FGs were assessed by a cytopathic effect assay and an HIV-1 p24 detection assay. The biomolecule interactions were explored via biolayer interferometry technology. The SAR was established by comparing its anti-HIV-1 activities, conserved CD4 induced (CD4i) epitope-dependent interactions and anticoagulant activities. Results FG efficiently and selectively inhibited the X4- and R5X4-tropic HIV-1 infections in C8166 cells with little cytotoxicity against C8166 cells and PBMCs. Our data indicated that FG bound to gp120 with nanomolar affinity and may interact with CD4i of gp120. Additionally, the CD4i binding affinity of FG was higher than that of dextran sulfate. SAR studies suggested that the unique sulfated fucose branches account for the anti-HIV-1 activity. The molecular size and present carboxyl groups of FG may also play important roles in various activities. Notably, several FG derivatives showed higher anti-HIV-1 activities and much lower anticoagulant activities than those of heparin. Conclusions FG exhibits strong activity against X4- and R5X4-tropic HIV-1 infections. The mechanism may be related to targeting CD4i of gp120, which results in inhibition of HIV-1 entry. The carboxyl group substituted derivatives of FG (8.5–12.8 kDa), might display high anti-HIV-1 activity and low anticoagulant activity. General significance Our data supports further the investigation of FG derivatives as novel HIV-1 entry inhibitors targeting CD4i.
研究领域:
病毒学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Tropical Medicine and Infectious Disease
·
2023
·Vol. 8
·期 2
·105
·
IF 2.9
Fengyu Tian,Cong Jin,Shangzhi Ji,Yanqing Tie,Guohao Fan,Ruiqing Zhang,Yehuan Zheng,Xinxin Shen,Xuejun Ma,Zhishan Feng
Human immunodeficiency virus 1 (HIV-1) attacks the immune system, making people susceptible to various diseases, thus increasing their risk of death. Comprehensive detection of major HIV-1 strains circulating in China is vital for effective HIV-1 infection prevention and treatment. HIV-1 nucleic acid detection is considered effective for HIV-1 diagnosis since traditional immunological testing may fail to detect HIV-1 infection during the window period. This work demonstrates a one-pot two-stage amplification assay (RT-RAP), a combination of reverse transcription recombinase (RT- RAA), and quantitative real-time polymerase chain reaction (qRT-PCR). The turn-around time of the assay is only 50 min and can be performed with commonly available laboratory equipment, the qPCR devices. The RT-RAP assay could detect approximately 5 and 14 copies/reaction of HIV-1 DNA and RNA using recombinant plasmids and standard reference strains, respectively. Additionally, we found that the clinical performance of RT-RAP (detected 169 samples out of 170 specimens) was consistent with that of qRT-PCR. The sensitivity and specificity of RT-RAP were 100.00% (99/99) and 98.59% (70/71), respectively, while its positive and negative predictive values were 99.00% (99/100) and 100.00% (70/70), respectively. The total coincidence rate of the RT-RAP was 99.41% (169/170), with a kappa value of 0.988 (p< 0.05). We demonstrated that RT-RAP could rapidly detect the common HIV-1 subtypes commonly circulating in China with comparable sensitivity and specificity to qRT-PCR.Keywords:HIV-1;RT-RAA;qRT-PCR;clinical detection
研究领域:
病毒学
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分子生物学
·
临床诊断
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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
ACS Omega
·
2024
·
IF 3.7
Komal Hayat,Gemma Nixon,Qian Zhang,Magdalini Matziari
A highly efficient method to synthesize diverse symmetrical phosphinic acids with the potential to act as pivotal candidates in the design of HIV-1 protease inhibitors has been developed. Such compounds have been designed based on the enzyme–substrate specificity, and their elongated analogues are expected to demonstrate significant inhibition against the HIV-1 protease with IC50 values in the low nanomolar range. Moreover, a highly efficient esterification protocol with carbohydrates and flavonoids has been devised to address the inherent absorption challenges associated with phosphinic-based drugs. These esters not only exhibit low toxicity but also have the potential to generate flavonoid moieties in situ, which are associated with hepatoprotective effects, or naturally occurring carbohydrate metabolites. The methodology utilizes effective peptide coupling reagents, such as aminium-based TBTU and carbodiimide-based DIC, and affords the target products in excellent to quantitative yields. This research represents a promising avenue for the development of novel HIV-1 protease inhibitors with significant therapeutic benefits.
研究领域:
药物化学
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生物化学
·
抗病毒研究
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2024
·
IF 5.7
Mengmeng Wu,Bing Yang,Lu Shi,Qiaorong Tang,Jing Wang,Wei Liu,Baoxin Li,Yan Jin
Background The human immunodeficiency virus (HIV) remains a major worldwide health problem. Nowadays, many methods have been developed for quantitative detecting human immunodeficiency virus DNA (HIV-DNA), such as fluorescence and colorimetry. However, these methods still have the disadvantages of being expensive and requiring professional technicians. Early diagnosis of pathogens is increasingly dependent on portable instruments and simple point-of-care testing (POCT). Therefore, it is meaningful and necessary to develop portable and cheap methods for detecting disease markers. Results In this work, a label-free chemiluminescence (CL) method was developed for detecting HIV-DNA via a handheld luminometer. To achieve label-free target detection, the CL catalyst, G-triplex-hemin DNAzyme (G3-hemin DNAzyme), was in-situ assembled in the presence of HIV-DNA. For improving sensitivity, HIV-DNA induced the cyclic strand displacement reaction (SDR), which can form three G3-hemin DNAzymes in one cycle. So, the chemiluminescence reaction between luminol and H 2 O 2 was highly effectively catalyzed, and the CL intensity was linearly related with the concentration of HIV-DNA in the range of 0.05–10 nM with a detection limit of 29.0 pM. Due to the high specificity of hairpin DNA, single-base mismatch can be discriminated, which ensured the specific detection of HIV-DNA. Significance In-situ formation of G3-hemin DNAzyme led to label-free and selective detection without complex synthesis and functionalization. Therefore, it offers a cheap, selective, sensitive and portable method for detecting disease-related genes, which is promising for POCT of clinical diagnosis in resource-limited settings.
研究领域:
生物医学
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分子诊断
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临床检验
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DOI
PubMed
高影响因子
Nanoscale
·
2018
·Vol. 10
·期 12
·5532-5538
·
IF 7.233
Bi-Yun Fang,Cheng Li,Jie An,Sun-Duo Zhao,Zhi-Yong Zhuang,Yuan-Di Zhao,Yue-Xuan Zhang
In this paper, DNA containing six cytosines as the formation site for silver nanoclusters (Ag NCs) was adopted as a template for preparing fluorescent DNA-Ag NCs. For the first time, it was found that the fluorescence of DNA-Ag NCs could be quenched after hybridization with their complementary sequence. On the basis of this new phenomenon, we designed a sequence C1 that was completely complementary to human immunodeficiency virus (HIV) DNA, and probe DNA which was partially complementary to C1 for the synthesis of DNA-Ag NCs. The fluorescence of DNA-Ag NCs was quenched after hybridization with C1 and the DNA-Ag NCs/C1 composite was formed, while C1 could be dissociated away from the DNA-Ag NCs by HIV DNA through a strand exchange reaction due to the stronger affinity between HIV DNA and C1, which could switch on the quenched Ag NCs, thus a new “off–on” fluorescence method for HIV DNA detection was developed. In the experiment, the Ag NCs formation site of DNA, the number of base pairs, and the pH and salt concentration of binding buffer were optimized. Under the optimum conditions, the limit of detection for HIV DNA was obtained to be 3.18 nM (3σ/N, n = 7) with the linear range of 15–150 nM for the 150 nM DNA-Ag NCs/C1 probe. Besides, the probe showed excellent specificity to HIV DNA, and even distinguished one nucleotide mismatched HIV DNA.
研究领域:
生物技术
·
纳米技术
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分子生物学
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病毒学
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产品关联
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2023
·
IF 4.8
Lilin Qin,Fangxu Lou,Yan Wang,Yinhao Zhang,Shishi Liu,Xu Hun
Molecular switches formed by enzyme-DNA hybrid compounds combined with CRISPR-Cas12a cis -cleavage used for photoelectrochemical nucleic acid assay was fabricated. A compound, molecular switch, consisting of Taq DNA polymerase, aptamer, block DNA and methylene blue labeled primer (primer-Mb) is formed. Block DNA is assembled on the surface of MBs (block DNA-MBs), and hybridized with the primer-Mb. In the presence of Human Immunodeficiency Virus (HIV) target, molecular switches are turned on by hybridization of the target with block DNA. The Taq DNA polymerase is released and activated. The activated Taq DNA polymerase elongates the primer via the template, block DNA, which attached onto Magnetic beads (MBs). A dsDNA with Mb (dsDNA-Mb) was formed. With the assistance of Cas12a, a amplified photoelectrochemical signal was obtained and the HIV target DNA was qualified. Under the best conditions, the limit of detection (LOD) can be as low as 0.3 fM. This photoelectrochemical assay extends the tool kit of molecular nanotechnology.
研究领域:
分子生物学
·
生物化学
·
纳米技术
·
病毒学
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DOI
高影响因子
Tissue Barriers
·
2024
·
IF 3.6
Qi Cao,Wei Zeng,Jingmin Nie,Yongjun Ye,Yanchao Chen
Impairment of the blood – brain barrier (BBB) and subsequent inflammatory responses contribute to the development of human immunodeficiency virus (HIV)-1-associated neurocognitive disorders (HAND). Apelin-13, the most abundant member of the apelin family, acts as the ligand of the angiotensin receptor-like 1 (APJ). However, its pharmacological function in HAND and its underlying mechanism are unknown. In the current study, we report that the presence of HIV-1 Tat reduced the levels of Apelin-13 and APJ in the cortex tissue of mice. Importantly, Apelin-13 preserved BBB integrity against HIV-1 Tat in mice by increasing the expression of the tight junction protein zonula occludens-1 (ZO-1) and occludin. Interestingly, increased macrophage infiltration, indicated by elevated CD68-positive staining was observed in the cortex after stimulation with HIV-1, which was mitigated by the administration of Apelin-13. Correspondingly, Apelin-13 reduced the expression of monocyte chemoattractant protein-1; (MCP-1). An in vitro two-chamber and two-cell trans-well assay demonstrated that HIV-1 Tat challenge significantly promoted macrophage migration, which was notably attenuated by the introduction of Apelin-13. Accordingly, treatment with Apelin-13 restored the HIV-1 Tat-induced reduction of occludin and ZO-1, while preventing the upregulation of MCP-1 in human brain microvascular endothelial cells (HBMVECs). Our results suggest that Apelin-13 may reduce macrophage infiltration into brain tissues and mitigate BBB dysfunction in patients with HAND.
研究领域:
神经科学
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免疫学
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药理学
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DOI
PubMed
高影响因子
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