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RNA interference:Antiviral weapon and beyond 被引量:14
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作者 Quan-Chu Wang Qing-He Nie Zhi-Hua Feng, The Center of Diagnosis and Treatment for Infectious Diseases of Chinese PLA, Tangdu Hospital, Fourth Military Medical University, Xi’an 710038, Shaanxi Province, China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2003年第8期1657-1661,共5页
RNA interference (RNAi) is a remarkable type of gene regulation based on sequence-specific targeting and degradation of RNA. The term encompasses related pathways found in a broad range of eukaryotic organisms, includ... RNA interference (RNAi) is a remarkable type of gene regulation based on sequence-specific targeting and degradation of RNA. The term encompasses related pathways found in a broad range of eukaryotic organisms, including fungi, plants, and animals. RNA interference is part of a sophisticated network of interconnected pathways for cellular defense, RNA surveillance, and development and it may become a powerful tool to manipulate gene expression experimentally. RNAi technology is currently being evaluated not only as an extremely powerful instrument for functional genomic analyses, but also as a potentially useful method to develop specific dsRNA based gene-silencing therapeutics.Several laboratories have been interested in using RNAi to control viral infection and many reports in Nature and in Cell show that short interfering (si) RNAs can inhibit infection by HIV-1, polio and hepatitis C viruses in a sequence-specific manner. RNA-based strategies for gene inhibition in mammalian cells have recently been described, which offer the promise of antiviral therapy. 展开更多
关键词 RNA干涉技术 基因治疗 滤过性病原体 人免疫缺陷 乙型肝炎
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Negative feedback regulation of cellular antiviral signaling by RBCKl-mediated degradation of IRF3 被引量:13
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作者 Min Zhang Yang Tian +6 位作者 Rui-Peng Wang Dong Gao Yan Zhang Fei-Ci Diao Dan-Ying Chen Zhong-HeZhai Hong-Bing Shu 《Cell Research》 SCIE CAS CSCD 2008年第11期1096-1104,共9页
Viral infection causes host cells to produce type I interferons (IFNs), which are critically involved in viral clearance. Previous studies have demonstrated that activation of the transcription factor interferon reg... Viral infection causes host cells to produce type I interferons (IFNs), which are critically involved in viral clearance. Previous studies have demonstrated that activation of the transcription factor interferon regulatory factor (IRF)3 is essential for virus-triggered induction of type I IFNs. Here we show that the E3 ubiquitin ligase RBCC protein interacting with PKC1 (RBCK1) catalyzes the ubiquitination and degradation of IRF3. Overexpression of RBCK1 negatively regulates Sendai virus-triggered induction of type I IFNs, while knockdown of RBCK1 has the opposite effect. Plaque assays consistently demonstrate that RBCKI negatively regulates the cellular antiviral response. Furthermore, viral infection leads to induction of RBCK1 and subsequent degradation of IRF3. These findings suggest that the cellular antiviral response is controlled by a negative feedback regulatory mechanism involving RBCKl-mediated ubiquitination and degradation of IRF3. 展开更多
关键词 RBCK1 IRF3 antiviral response type I IFNs feedback regulation E3 ligase
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YMDD mutations in patients with chronic hepatitis B untreated with antiviral medicines 被引量:9
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作者 Zhong-MinHuang Qi-WenHuang Ya-QinQin Yan-ZhuanHe Hou-JiQin Yiao-NanZhou XiangXu Mei-JinHuang 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第6期867-870,共4页
AIM: To polymerase P region (YMDD) mutations of hepatitis B virus gene (HBV DNA) in patients with chronic hepatitis B (CHB) untreated with antiviral medicines and to explore its correlation with pre-c-zone mutations, ... AIM: To polymerase P region (YMDD) mutations of hepatitis B virus gene (HBV DNA) in patients with chronic hepatitis B (CHB) untreated with antiviral medicines and to explore its correlation with pre-c-zone mutations, HBV genotypes and HBV DNA level, and to observe its curative effect.METHODS: A total of 104 cases (38 cases in group of familial aggregation and 66 cases in group of non-familial aggregation) were randomly chosen from 226 patients with CHB who did not receive the treatment of lamivudine (LAM)and any other antivirus drugs within the last one year.Their serum YMDD mutations were detected by microcosmic nucleic acid and cross-nucleic acid quantitative determination,HBV genotypes by PCR-microcosmic nucleic acid crossELISA, HBV DNA quantitative determination and fluorescence ration PCR analysis, hepatitis B virus markers (HBVM) by ELISA. LAM was taken by 10 patients with YMDD mutations and its curative effect was observed.RESULTS: Twenty-eight cases (26.9%) had YMDD mutations, of them 11 cases (28.9%) were in familial aggregation group (38 cases) and 17 cases (25.8%) in nonfamilial aggregation group (66 cases) with no significant difference between the two groups. Twenty-seven point one percent (16/59) cases were positive for HBeAg YMDD mutations, and 26.7% (12/45) cases were negative for HBeAg and positive for anti-HBe. There was also no significant difference between the two groups. Different YMDD incidence rate existed in different HBV genotypes.HBV DNA level did not have a positive correlation with the incidence of YMDD mutations. LAM was effective for all patients with mutations.CONCLUSION: Wild mutant strains in HBV and their incidence rate have no significant difference between familial aggregation and non-familial aggregation. It may have no significant relationship between YMDD mutations and pre-c-zone mutations. HBV DNA level may not have a positive correlation with YMDD mutations. LAM is clinically effective for CHB patients with YMDD mutations. 展开更多
关键词 Hepatitis B virus Chronic hepatitis GENOTYPES YMDD mutation LAMIVUDINE
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Improvement of quantitative testing of liver function in patients with chronic hepatitis C after installment of antiviral therapy 被引量:8
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作者 Matthias Ocker Marion Ganslmayer +4 位作者 Steffen Zopf Susanne Gahr Christopher Janson Eckhart G. Hahn Christoph Herold 《World Journal of Gastroenterology》 SCIE CAS CSCD 2005年第35期5521-5524,共4页
MM: To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function (QTLF). METHODS: Fifty patients with chronic hepatitis C were either treated with inter... MM: To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function (QTLF). METHODS: Fifty patients with chronic hepatitis C were either treated with interferon (n = 8), interferon/ribavirin (n = 19) or peg-interferon/ribavirin (n = 23). Quantitative testing of liver function, including aminopyrine breath test (ABT), galactose elimination capacity (GEC), sorbitol clearance (SCI) and indocyanine green clearance (ICG) was performed before and 3 mo after initiation of antiviral therapy. RESULTS: After 3 mo of antiviral treatment, 36 patients showed normal transaminases and were negative for HCVRNA, 14 patients did not respond to therapy. ABT and GEC as parameters of microsomal and cytosolic liver function were reduced in all patients before therapy initiation and returned to normal values in the 36 therapy responders after 3 too. Parameters of liver perfusion (SCl and ICG) were not affected by antiviral therapy. In the 14 non-responders, no changes in QTLF values were observed during the treatment period. CONCLUSION: ICG and SCI remained unaffected in patients with chronic hepatitis C, while ABT and GEC were significantly compromised. ABT and GEC normalized in responders to antiviral therapy. Early determination of ABT and GEC may differentiate responders from non-responders to antiviral treatment in hepatitis C. 展开更多
关键词 Aminopyrine breath test Galactose eliminationcapacity Indocyanine green clearance Sorbitol clearance Hepatitis C Interferon RIBAVIRIN
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Antiviral Effect of Interferon-Induced Guanylate Binding Protein-1 against Coxsackie Virus and Hepatitis B Virus B3 in Vitro 被引量:4
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作者 Yin-ping LU  Bao-ju WANG  +4 位作者 Ji-hua DONG  Zhao LIU  Shi-he GUAN  Meng-ji LU   Dong-liang YANG 《中国病毒学》 CSCD 2007年第3期193-198,共6页
Guanylate binding protein-1(GBP-1)is an interferon-induced protein.To observe its antiviral effect against Hepatitis B virus(HBV)and Coxsackie virus B3(CVB3),we constructed an eukaryotic expression vector of human GBP... Guanylate binding protein-1(GBP-1)is an interferon-induced protein.To observe its antiviral effect against Hepatitis B virus(HBV)and Coxsackie virus B3(CVB3),we constructed an eukaryotic expression vector of human GBP-1(hGBP-1).Full-length encoding sequence of hGBP-1 was amplified by long chain RT-PCR and inserted into a pCR2.1 vector,then subcloned into a pCDNA3.1(-)vector.Recombinant hGBP-1 plasmids and pHBV1.3 carrying 1.3-fold genome of HBV were contransfected into HepG2 cells,and inhibition effect of hGBP-1 against HBV replication was observed.Hela cells transfected with recombinant hGBP-1 plasmids were challenged with CVB3,and viral yield in cultures were detected.The results indicated that recombinant eukaryotic expression plasmid of hGBP-1 was constructed successfully and the hGBP-1 gene carried in this plasmid could be efficiently expressed in HepG2 cells and Hela cells.hGBP-1 inhibit CVB3 but not HBV replication in vitro.These results demonstrate that hGBP-1 mediates an antiviral effect against CVB3 but not HBV and perhaps plays an important role in the interferon-mediated antiviral response against CVB3. 展开更多
关键词 柯萨奇 干扰素 乙型肝炎 滤过性病原体 鸟苷酸结合蛋白质
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Establishment of a cell-based assay system for hepatitis C virus serine protease and its primary applications 被引量:3
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作者 Hong-Xia Mao Shui-Yun Lan Yun-Wen Hu Li Xiang Zheng-Hong Yuan, Key Laboratory of Medical Molecular Virology, Shanghai Medical College, Fudan University, Shanghai 200032, China 《World Journal of Gastroenterology》 SCIE CAS CSCD 2003年第11期2474-2479,共6页
AIM: To establish an efficient, sensitive, cell-based assay system for NS3 serine protease in an effort to study further the property of hepatitis C virus (HCV) and develop new antiviral agents.METHOOS: We constructed... AIM: To establish an efficient, sensitive, cell-based assay system for NS3 serine protease in an effort to study further the property of hepatitis C virus (HCV) and develop new antiviral agents.METHOOS: We constructed pCI-neo-NS3/4A-SEAP chimeric plasmid, in which the secreted alkaline phosphatase (SEAP) was fused in-frame to the downstream of NS4A/4B cleavage site. The protease activity of NS3 was reflected by the activity of SEAP in the culture media of transient or stable expression cells. Stably expressing cell lines were obtained by G418 selection. Pefabloc SC, a potent irreversible serine protease inhibitor, was used to treat the stably expressing cell lines to assess the system for screening NS3 inhibitors. To compare the activity of serine proteases from 1b and 1a, two chimeric clones were constructed and introduced into both transient and stable expression systems.RESULTS: The SEAP activity in the culture media could be detected in both transient and stable expression systems,and was apparently decreased after Pefabloc SC treatment.In both transient and stable systems, NS3/4A-SEAP chimeric gene from HCV genotype 1b produced higher SEAP activity in the culture media than that from 1a.CONCLUSION: The cell-based system is efficient and sensitive enough for detection and comparison of NS3 protease activity, and screening of anti-NS3 inhibitors. The functional difference between NS3/4A from 1a and 1b subtypes revealed by this system provides a clue for further investigations. 展开更多
关键词 丙型肝炎 丝氨酸蛋白酶 滤过性病原体 NS3蛋白酶 细胞基础分析系统
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Bio-mathematical models of viral dynamics to tailor antiviral therapy in chronic viral hepatitis 被引量:1
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作者 Maurizia Rossana Brunetto Piero Colombatto Ferruccio Bonino 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第5期531-537,共7页
The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe... The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral hepatitis describe the viral load decline in the f irst 2-4 wk of antiviral therapy, but do not adequately simulate the dynamics of viral infection for the following period. The hypothesis of a constant clearance rate of the infected cells provides an unrealistic estimation of the time necessary to reach the control or the clearance of hepatitis B virus (HBV)/ hepatitis C virus (HCV) infection. To overcome the problem, we have developed a new multiphasic model in which the immune system activity is modulated by a negative feedback caused by the infected cells reduction, and alanine aminotransferase kinetics serve as a surrogate marker of infected-cell clearance. By this approach, we can compute the dynamics of infected cells during the whole treatment course, and find a good correlation between the number of infected cells at the end of therapy and the long-term virological response in patients with chronic hepatitis C. The new model successfully describes the HBV infection dynamics far beyond the third month of antiviral therapy under the assumption that the sum of infected and non-infected cells remains roughly constant during therapy, and both target and infected cells concur in the hepatocyte turnover. In clinical practice, these new models will allow the development of simulators of treatment response that will be used as an "automatic pilot" for tailoring antiviral therapy in chronic hepatitis B as well as chronic hepatitis C patients. 展开更多
关键词 Viral hepatitis Bio-mathematical models Hepatitis B virus Hepatitis C virus Viral dynamics
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Antiviral effect of polysaccharide from Spirulina platensis(PSP) on HSV-2 in vitro 被引量:1
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作者 HONG YU XIAO ZHU WEN QING ZHANG RUI Lü 《Journal of Microbiology and Immunology》 2006年第2期146-152,共7页
To explore the antiviral effect and mechanism of polysaccharide from Spirulina platensis (PSP) on herpes simplex virus type 2 (HSV-2), a standard strain of HSV-2 (333 strain) was used to investigate the antivira... To explore the antiviral effect and mechanism of polysaccharide from Spirulina platensis (PSP) on herpes simplex virus type 2 (HSV-2), a standard strain of HSV-2 (333 strain) was used to investigate the antiviral effect of PSP in vitro. PSP in various concentrations was applied to different stages of HSV-2 replication cycle. Finally, the virus infectivity (TCID50), cytopathic effect (CPE), and MTT staining method for viable cells (MTT assay) were used as markers to evaluate the effect of PSP on HSV-2. The quantity of HSV-DNA was detected by real-time fluorescence quantitative PCR (FQ-PCR). The HSV-2 infected Vero cell tdtrastructures were observed by transmission electron microscopy (TEM). The results showed that PSP had little cytotoxic effect on Vero cells, it could not directly inactivate HSV-2 infectivity. PSP not only interfered in adsorption of HSV-2 to Vero cells but also inhibited HSV-2 biosynthesis in the ceils. FQ-PCR results showed that the inhibitory rate on HSV- DNA also increased in a dose-dependent and time-dependent manner. TEM also confirmed that PSP exhibited pronounced inhibitory effect on HSV-2. In conclusion, the antiviral effect of PSP on HSV-2 may be attributed to the inhibition of virus adsorption, virus replication and synthesis in cells. 展开更多
关键词 Polysaccharide from Spirulina platensis (PSP) HSV-2 FQ-PCR TEM
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Solid lipid nanoparticles loading adefovir dipivoxil for antiviral therapy 被引量:1
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作者 Min-wei LI Jing MIAO +2 位作者 Sai-ping JIANG Fu-qiang HU Yong-zhong DU 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2008年第6期506-510,共5页
Herein,solid lipid nanoparticles(SLN)were proposed as a new drug delivery system for adefovir dipivoxil(ADV). The octadecylamine-fluorescein isothiocynate(ODA-FITC)was synthesized and used as a fluorescence maker to b... Herein,solid lipid nanoparticles(SLN)were proposed as a new drug delivery system for adefovir dipivoxil(ADV). The octadecylamine-fluorescein isothiocynate(ODA-FITC)was synthesized and used as a fluorescence maker to be incorporated into SLN to investigate the time-dependent cellular uptake of SLN by HepG2.2.15.The SLN of monostearin with ODA-FITC or ADV were prepared by solvent diffusion method in an aqueous system.About 15 wt%drug entrapment efficiency(EE)and 3 wt% drug loading(DL)could be reached in SLN loading ADV.Comparing with free ADV,the inhibitory effects of ADV loaded in SLN on hepatitis B surface antigen(HBsAg),hepatitis B e antigen(HBeAg)and hepatitis B virus(HBV)DNA levels in vitro were significantly enhanced. 展开更多
关键词 Adefovir dipivoxil (ADV) Solid lipid nanoparticles (SLN) Octadecylamine-fluorescein isothiocynate (ODA-FITC) Hepatitis B virus (HBV)
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Stereoselective Total Synthesis of Mycalamides
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作者 Masahiro Toyota 《复旦学报(自然科学版)》 CAS CSCD 北大核心 2005年第5期813-814,共2页
关键词 立体选择 微生物 滤过性病原体 菌素 免役抑制
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Effect of Traditional Chinese Medicine Antiviral Capsules On Animal Model Genital Herpes and HSV-2 in Cell Culture
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作者 范瑞强 李红毅 +2 位作者 谢长才 禤国维 朱宇同 《Chinese Journal of Sexually Transmitted Infections》 2001年第2期29-33,共5页
Objective: To study the effect of traditional Chinese medicine antiviral capsules in the treatment of genital herpes. Methods: Using female guinea pig genital herpes as the animal model, this study used oral administr... Objective: To study the effect of traditional Chinese medicine antiviral capsules in the treatment of genital herpes. Methods: Using female guinea pig genital herpes as the animal model, this study used oral administration of two formulations of antiviral capsules (AC) and observed the effect on vaginal HSV-2 titers and vulvar symptoms. Cell cultures were also used to examine the direct inactivation of HSV-2 by the antiviral capsules and the suppression of HSV-2 via three drug administration methods. Results: There was no significant difference of mean vaginal virus titers between the antiviral capsule groups and that of the positive acyclovir (ACV) control (P>0.05). Mean vulvarsymptom scores of the two antiviral capsule groups were also significantly lower than that of the saline negative control group on days 2, 3, 5, 7 and 8 (P<0.05) and similar to that of the ACV control (P>0.05). Cell culture showed the minimum inhibitory concentrations of antiviral capsules No. 1 and No. 2 were 0.390625 mg/ml and 1.5625 mg/ml, respectively. Conclusion: The traditional Chinese medicine antiviral capsules had suppressive effects on HSV-2 in both animal model GH and in vitro cell culture. 展开更多
关键词 Chinese Herbs Genital Herpes/Animal Model Cell Culture
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Antiviral and analgesic activity of the complex of Hypericum Perforatum L extract and Lysine monohydrochloride
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作者 HuRan KuBaoshan JiaYongrui ZhangYonghe 《中国药理通讯》 2004年第2期51-51,共1页
Objective: To screen the antiviral and analgesic activities of the complex of extract of Hypericum Perforatum L (EHPL) and Lysine hydrochloride in mass ratio of 1: 1, 1: 2 and 2: 1 to determinewhich one is better. Met... Objective: To screen the antiviral and analgesic activities of the complex of extract of Hypericum Perforatum L (EHPL) and Lysine hydrochloride in mass ratio of 1: 1, 1: 2 and 2: 1 to determinewhich one is better. Methods: In screening test, the antiviral activities on herpes simplex virus type 展开更多
关键词 滤过性病原体 止痛剂 金丝桃属植物提取物 赖氨酸 高效液相色谱法
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