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
·
代谢学
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HIV/AIDS研究
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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
·
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
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药物开发
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PubMed
高影响因子
Tissue Barriers
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2024
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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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PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2022
·
IF 6.911
Xiaofen Zhao,Xiaoxiao Tian,Yuwei Wang,Linbin Li,Yan Yu,Shiqiao Zhao,Juan Zhang
Accurate analysis of HIV DNA is valuable for the diagnosis of AIDS. Herein, an ultrasensitive and specific fluorescence method was developed for HIV-1 DNA detection based on CRISPR-Cas12a-activated palindrome-catalytic hairpin assembly (CRISPR-Cas12a-PCHA). The presence of HIV-1 DNA activated the trans-cleavage activity of CRISPR-Cas12a, which could continuously digest the DNA fragment of hairpins connected to magnetic beads to expose single-stranded RNA . After magnetic separation, the exposed RNA triggered multiple PCHA reactions, generating many Y-shaped DNA structures that were self-assembled into the DNA superstructures via the hybridization of palindromic sticky ends, leading to the release of amounts of fluorescence signal. Different from the reported recently biosensing strategies of nucleic acid amplification technologies-activated CRISPR-Cas12a, CRISPR-Cas12a-PCHA endowed the strategy with unique advantages of simple sample pretreatment , direct duplex target detection, and ultrahigh sensitivity. The strategy was able to resist the interference of the complex matrix in real sample and distinguish between HIV patients and healthy persons. Thus, the method is a promising tool for ultrasensitive and specific detection of HIV-1 DNA for AIDS diagnosis.
研究领域:
生物技术
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分子生物学
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医学诊断
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PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
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2020
·
IF 7.1
Hui Kong,Wei Zhang,Jia Yao,Chao Li,Renfei Lu,Zhen Guo,Jinze Li,Chuanyu Li,Yingxue Li,Chiyu Zhang,Lianqun Zhou
Development of a simple, sensitive and specific method for HIV-1 assay is demanded. In some emergency situations, a portable reverse transcription loop-mediated isothermal amplification (RT-LAMP) platform is necessary. A novel hydrogen ion-selective RT-LAMP (H + -RT-LAMP) sensor was developed for highly sensitive HIV-1 using hydrogen ion concentration as a signal producing compound. The H + -RT-LAMP sensor was based on screen-printed with carbon-doped graphene conductive layer, carbon nanotubes (CNTs) solid electrolyte layer, and reference electrode KCl functional layer, which provided superior electrical signals, high sensitivity and stability for HIV-1 detection. The rate of hydrogen ion production was related to the viral load (VL) during the amplification of HIV-1. The sensitive HIV-1 RNA detection range was achieved from 0 copies/μL to 10 5 copies/μL. The proposed H + -RT-LAMP sensor was applied to detect HIV-1 RNA in real human serum. 57 samples were detected and satisfactory results were obtained. Compared with commercial instruments, the detection results of H + -RT-LAMP sensor demonstrated a perfect concordance rate of 96.5 %, and the limit of detection (LOD) for the clinical samples was 10 copies per tube. Time to get the result is from 10 min to 25 min. Therefore, the proposed H + -RT-LAMP sensor was particularly suitable as a point-of-care device for the on-site detection of HIV-1.
研究领域:
分子生物学
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医学检验
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生物传感器
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DOI
高影响因子
Natural Product Communications
·
2022
·
IF 1.496
Qing Liu,Ying Wei,Yongjia Hao,Jian Yang,Bowen Pan,Xiaosheng Yang,Ying Zhou,Xia Wang
Viral infection imposes a major threat to human health. To develop new potent antiviral agents, Hederagenin (HE), a known inhibitor of HIV-1 and HCV NS3/4A proteases, was used as a starting material to synthesize 4 types of HE derivatives, HE-3,23-diacyl, HES-3,23-diacyl, HES-3-acyl, and HES-3-oxo-23-acyl. We evaluated the in vitro inhibitory activities of the derivatives against HIV-1 and HCV NS3/4A proteases. (3β,23)-Di-O-diglutaryl-hederagenin (1b) and (3β,23)-di-O-(3′,3′-dimethylsuccinyl-hederagenin ethyl ester (2b) exhibited potent inhibitory activities against the HIV-1 and/or HCV NS3/4A proteases with IC50 values < 10 μM, but did not appreciably inhibit general human proteases renin and trypsin. The SARs showed that dicarboxylic acid hemiesters of HE significantly enhance the antiviral activities when C3 or C23 are linked with 6 carbon acyl chains.
研究领域:
药理学
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病毒学
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药物化学
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高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2016
·Vol. 408
·期 22
·6115-6121
·
IF 3.125
Zhang Yun,Yang Hang,Yu Junping,Wei Hongping
In this study, a system of magnetic beads (MBs) coupled with catalytic fluorescent immunoassay for rapid and sensitive determination of HIV-1 capsid antigen p24 was developed. p24 was captured by antibody immobilized MBs, and the detection antibody was linked to horseradish peroxidase (HRP) through biotin–streptavidin recognition, catalyzing the oxidation of o -phenylenediamine (OPD) and hydrogen peroxide to produce a fluorescent product. This is the first reported utilization of the fluorescence of OPD oxidation product catalyzed by HRP for immunoassay. Optimization of conditions afforded a low detection limit of 0.5 pg/mL (3σ) for p24 with a linear range of 1.4–90.0 pg/mL. The assay exhibited good reproducibility with a relative standard deviation (RSD) of 4.4 %, 4.7 %, and 5.0 % for detecting 1.4 pg/mL, 22.5 pg/mL, and 45.0 pg/mL p24, respectively. The assay can be completed in less than 90 min. Moreover, the proposed method was successfully applied to detect p24 in spiked serum. This method overcomes the interference of MBs to the fluorescence signal and demonstrated higher sensitivity for detection of p24 than conventional ELISA kits. The system could be applied for detecting other antigens with high sensitivity, rapidity, specificity, and simple operation.
A rapid and sensitive biosensing method coupling immunomagnetic separation and catalytic fluorescence for determination of HIV-1 p24 has been developed
研究领域:
医学诊断
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生物化学
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PubMed
高影响因子
JOURNAL OF INFECTIOUS DISEASES
·
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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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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高影响因子
Science of Advanced Materials
·
2014
·Vol. 6
·期 9
·1936-1942
·
IF 2.908
Li Xiang,Ding Xuelian,Wang Gongke,Zhou Yixuan,Hou Ruipeng,Gao Shuyan,Lu Yan
In this work, we have developed a simple and highly sensitive fluorescent biosensor for the detection of HIV-1 RNase H activity and inhibition by using graphene oxide (GO) as sensing platform. In our approach, a DNA-RNA substrate was prepared which a carboxy fluorescein (FAM) was labeled
at the 3 termini of single strand DNA. The FAM labeled DNA-RNA substrate preserves most of the fluorescence when mixed with GO. However, in the present of RNase H, RNase H can cleavage the RNA into fragments, resulting in the dissociation of ssDNA and mononucleotides. The fluorescence intensity
was greatly quenched after the addition of GO. Because of the super quenching ability of GO, the as-proposed method provides a wide linear range from 1.0 to 26.3 units mL–1 and a low detection limit of 0.6 units mL–1 for HIV-1 RNase H activity analysis. Additionally,
this approach shows potential for high-throughput screening of HIV-1 RNase H inhibitors. The method not only provides a universal platform for monitoring activity and inhibition of RNase H but also shows great potential in biological process researches, drug discovery, and clinic diagnostics.
研究领域:
生物技术
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分子生物学
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纳米技术
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病毒学
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药物发现
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DOI
高影响因子
ChemMedChem
·
2011
·Vol. 6
·期 9
·1654-1664
·
IF 3.306
Yan Liu,Zhuofeng Ke,Kwok Yiu Wu,Shuwen Liu,Wen-Hua Chen,Shibo Jiang,Zhi-Hong Jiang
Graphical Stopping HIV in its tracks! A series of betulinic acid–polyphenol conjugates were synthesized, with the aid of rational design by docking simulation, as novel HIV-1 fusion/entry inhibitors targeting gp41. These amphiphilic conjugates cooperatively interact with hydrophobic and hydrogen-bonding areas in the groove of the gp41 NHR trimeric coiled coil, demonstrating a promising strategy for the discovery of HIV-1 fusion/entry inhibitor binding to these two crucial pockets. Exploration of potent inhibitors of the HIV-1 gp41 fusion core formation is a promising strategy to discover small-molecule HIV-1 entry inhibitors for the treatment of HIV-1 infection. In this paper, a series of novel betulinic acid–polyphenol conjugates was designed, guided by molecular modeling of the binding of betulinic acid (BA) and phenolic galloyl/caffeoyl groups in the groove on the gp41 N-terminal heptad repeat (NHR) trimeric coiled coil. These conjugates were synthesized via conjugation of galloyl and caffeoyl groups with BA at the C-28 position. Their inhibitory activities of HIV gp41 six-helix bundle (6-HB) formation between the NHR peptide N36 and the C-terminal heptad repeat (CHR) peptide C34 were evaluated with size-exclusion HPLC. Conjugates bearing a galloyl group were found to exhibit four to sixfold higher inhibitory activities than that of parent compound BA, suggesting that they may be exploitable as HIV-1 fusion/entry inhibitors targeting gp41. The docking study on BA and its derivatives suggests that hydrophobic and hydrogen-bonding pockets exist in the groove of the gp41 NHR trimeric coiled coil and that a potent inhibitor should have amphiphilic structures to cooperatively interact with both pockets. This possibility was explored by incorporating both lipophilic and hydrophilic groups into the conjugates in a well-defined orientation to bind with both pockets in the gp41 NHR-trimer.
研究领域:
药物化学
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病毒学
·
分子生物学
·
药理学
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PubMed
高影响因子
危险品化学品经营许可证（带存储）