Several receptors have been identified as implicated on viral entry into the hepatocyte; and, this interaction between the virus and potential receptors could modulate infection, spontaneous viral clearance, persisten...Several receptors have been identified as implicated on viral entry into the hepatocyte; and, this interaction between the virus and potential receptors could modulate infection, spontaneous viral clearance, persistence of the infection and the widespread of the virus as outbreak. Nevertheless, the playing role of each of them remains controversial. The NiemannPick type C1 like 1 gene (NPC1L1) receptor has been recently implicated on hepatitis C virus (HCV) entry into the cell and ezetimibe, an anti-cholesterol drug seems to block that, emerging the idea to control hepatitis C outbreak modulating lipid-related receptors. Hepatitis C infection seems to modulate lipid metabolism according to host genetic background. Indeed, it circulates like a lipoviroparticle. The main aim of this field of vision would be to discuss the role of hepatocyte receptors implicated on virus entry, especially NPC1L1 and the therapeutic options derived from the better knowledge about HCV-lipidsreceptors interaction.展开更多
Hepatitis C virus (HCV) infects more than three million new individuals worldwide each year. In a high percent age of patients, acute infections become chronic, eventually progressing to fibrosis, cirrhosis, and hepat...Hepatitis C virus (HCV) infects more than three million new individuals worldwide each year. In a high percent age of patients, acute infections become chronic, eventually progressing to fibrosis, cirrhosis, and hepatocellular carcinoma. Given the lack of effective prophylactic or therapeutic vaccines, and the limited sustained virological response rates to current therapies, new approaches are needed to prevent, control, and clear HCV infection.Entry into the host cell, being the first step of the viral cycle, is a potential target for the design of new antiviral compounds. Despite the recent discovery of the tight junction-associated proteins claudin-1 and occludin as HCV co-receptors, which is an important step towards the understanding of HCV entry, the precise mechanisms are still largely unknown. In addition, increasing evidence indicates that tools that are broadly employed to study HCV infection do not accurately reflect the real process in terms of viral particle composition and host cell phenotype. Thus, systems that more closely mimic natural infection are urgently required to elucidate the mechanisms of HCV entry, which will in turn help to design antiviral strategies against this part of the infection process.展开更多
目的:观察益气养阴化浊通络方对高糖诱导的小鼠肾足细胞自噬相关蛋白5(autophagy-related protein 5,ATG5)、B细胞淋巴瘤-2蛋白相互作用中心卷曲螺旋蛋白1(B-cell lymphoma-2-interacting myosin-like coiled-coil protein 1,Beclin-1)...目的:观察益气养阴化浊通络方对高糖诱导的小鼠肾足细胞自噬相关蛋白5(autophagy-related protein 5,ATG5)、B细胞淋巴瘤-2蛋白相互作用中心卷曲螺旋蛋白1(B-cell lymphoma-2-interacting myosin-like coiled-coil protein 1,Beclin-1)及B淋巴细胞瘤-2基因/腺病毒E1B相互作用蛋白3(B-cell lymphoma-2/adenovirus E1 B interacting protein 3,BNIP3)表达的影响,探讨其对自噬的作用。方法:选取Wistar大鼠,分别灌胃20,40,80 g·kg^(-1)益气养阴化浊通络方及生理盐水,制备低、中、高浓度含药血清和空白血清。体外培养小鼠肾足细胞,分为正常对照组、高糖组、益气养阴化浊通络方低、中、高剂量组和雷帕霉素组。CCK-8法检测细胞增殖,细胞划痕检测细胞迁移能力,qRT-PCR和Western blot检测微管相关蛋白1轻链3B(microtubule-associated protein 1 light chain 3 B,LC3B)、ATG5、Beclin-1及BNIP3 mRNA和蛋白表达。结果:与空白对照组相比,高糖组足细胞增殖减弱,迁移能力增强,LC3B、ATG5、Beclin-1及BNIP3 mRNA和蛋白表达显著减弱;与HG组相比,益气养阴化浊通络方低、中、高剂量含药血清组及雷帕霉素组均可促进足细胞增殖,抑制足细胞迁移,明显促进LC3B、ATG5、Beclin-1及BNIP3 mRNA和蛋白表达。结论:益气养阴化浊通络方能够促进高糖诱导的小鼠肾足细胞自噬,调节足细胞增殖及迁移。展开更多
In light of the scarcity of reports on the interaction between HSV-1 nucleocapsid protein UL25 and its host cell proteins,the purpose of this study is to use yeast two-hybrid screening to search for cellular proteins ...In light of the scarcity of reports on the interaction between HSV-1 nucleocapsid protein UL25 and its host cell proteins,the purpose of this study is to use yeast two-hybrid screening to search for cellular proteins that can interact with the UL25 protein.C9orf69,a protein of unknown function was identified.The interaction between the two proteins under physiological conditions was also confirmed by biological experiments including co-localization by fluorescence and immunoprecipitation.A preliminary study of the function of C9orf69 showed that it promotes viral proliferation.Further studies showed that C9orf69 did not influence viral multiplication efficiency by transcriptional regulation of viral genes,but indirectly promoted proliferation via interaction with UL25.展开更多
Viruses replicate and proliferate in host cells while continuously adjusting to and modulating the host environment.They encode a wide spectrum of multifunctional proteins,which interplay with and modify proteins in h...Viruses replicate and proliferate in host cells while continuously adjusting to and modulating the host environment.They encode a wide spectrum of multifunctional proteins,which interplay with and modify proteins in host cells.Viral genomes were chronologically the first to be sequenced.However,the corresponding viral proteomes,the alterations of host proteomes upon viral infection,and the dynamic nature of proteins,such as post-translational modifications,enzymatic cleavage,and activation or destruction by proteolysis,remain largely unknown.Emerging high-throughput techniques,in particular quantitative or semi-quantitative mass spectrometry-based proteomics analysis of viral and cellular proteomes,have been applied to define viruses and their interactions with their hosts.Here,we review the major areas of viral proteomics,including virion proteomics,structural proteomics,viral protein interactomics,and changes to the host cell proteome upon viral infection.展开更多
In this research paper, our main objective is to find out the meticulous role of activated dendritic cells （DCs） during the human immunodeficiency virus （HIV） infection process. DCs play a dual role by enhancing b...In this research paper, our main objective is to find out the meticulous role of activated dendritic cells （DCs） during the human immunodeficiency virus （HIV） infection process. DCs play a dual role by enhancing both HIV infection progression, as well as antiviral immune response. To explore the implications of these dual roles, we have formulated our mathematical model and analyzed the model by both analytical and numerical approaches. By using an impulsive differential equation, we have studied the effect of DC-based vaccination. Analytically we have determined the threshold value of drug dosage and dosing interval for optimum levels of injection. We have also investigated the effect of perfect adherence of drug dose on the immune cell count in extreme cases and observed that, systematic drug dose of the immune cells leads to its maximum level.展开更多
文摘Several receptors have been identified as implicated on viral entry into the hepatocyte; and, this interaction between the virus and potential receptors could modulate infection, spontaneous viral clearance, persistence of the infection and the widespread of the virus as outbreak. Nevertheless, the playing role of each of them remains controversial. The NiemannPick type C1 like 1 gene (NPC1L1) receptor has been recently implicated on hepatitis C virus (HCV) entry into the cell and ezetimibe, an anti-cholesterol drug seems to block that, emerging the idea to control hepatitis C outbreak modulating lipid-related receptors. Hepatitis C infection seems to modulate lipid metabolism according to host genetic background. Indeed, it circulates like a lipoviroparticle. The main aim of this field of vision would be to discuss the role of hepatocyte receptors implicated on virus entry, especially NPC1L1 and the therapeutic options derived from the better knowledge about HCV-lipidsreceptors interaction.
基金Supported by CIBERehd to Moreno-Otero R, López-Cabrera M and Majano PLSAF2007-61201 (Ministerio de Educación y Ciencia) to López-Cabrera M+3 种基金CP03/0020 (Instituto de Salud Carlos Ⅲ)SAF2007-60677 (Ministerio de Educación y Ciencia)PI10/00101 (Ministerio de Ciencia e Innovación, Instituto de Salud Carlos Ⅲ, FEDER) to Majano PL. Benedictosupported by CIBERehd and Molina-Jiménez F by Instituto de Salud Carlos Ⅲ and FIB Hospital de la Princesa
文摘Hepatitis C virus (HCV) infects more than three million new individuals worldwide each year. In a high percent age of patients, acute infections become chronic, eventually progressing to fibrosis, cirrhosis, and hepatocellular carcinoma. Given the lack of effective prophylactic or therapeutic vaccines, and the limited sustained virological response rates to current therapies, new approaches are needed to prevent, control, and clear HCV infection.Entry into the host cell, being the first step of the viral cycle, is a potential target for the design of new antiviral compounds. Despite the recent discovery of the tight junction-associated proteins claudin-1 and occludin as HCV co-receptors, which is an important step towards the understanding of HCV entry, the precise mechanisms are still largely unknown. In addition, increasing evidence indicates that tools that are broadly employed to study HCV infection do not accurately reflect the real process in terms of viral particle composition and host cell phenotype. Thus, systems that more closely mimic natural infection are urgently required to elucidate the mechanisms of HCV entry, which will in turn help to design antiviral strategies against this part of the infection process.
文摘目的:观察益气养阴化浊通络方对高糖诱导的小鼠肾足细胞自噬相关蛋白5(autophagy-related protein 5,ATG5)、B细胞淋巴瘤-2蛋白相互作用中心卷曲螺旋蛋白1(B-cell lymphoma-2-interacting myosin-like coiled-coil protein 1,Beclin-1)及B淋巴细胞瘤-2基因/腺病毒E1B相互作用蛋白3(B-cell lymphoma-2/adenovirus E1 B interacting protein 3,BNIP3)表达的影响,探讨其对自噬的作用。方法:选取Wistar大鼠,分别灌胃20,40,80 g·kg^(-1)益气养阴化浊通络方及生理盐水,制备低、中、高浓度含药血清和空白血清。体外培养小鼠肾足细胞,分为正常对照组、高糖组、益气养阴化浊通络方低、中、高剂量组和雷帕霉素组。CCK-8法检测细胞增殖,细胞划痕检测细胞迁移能力,qRT-PCR和Western blot检测微管相关蛋白1轻链3B(microtubule-associated protein 1 light chain 3 B,LC3B)、ATG5、Beclin-1及BNIP3 mRNA和蛋白表达。结果:与空白对照组相比,高糖组足细胞增殖减弱,迁移能力增强,LC3B、ATG5、Beclin-1及BNIP3 mRNA和蛋白表达显著减弱;与HG组相比,益气养阴化浊通络方低、中、高剂量含药血清组及雷帕霉素组均可促进足细胞增殖,抑制足细胞迁移,明显促进LC3B、ATG5、Beclin-1及BNIP3 mRNA和蛋白表达。结论:益气养阴化浊通络方能够促进高糖诱导的小鼠肾足细胞自噬,调节足细胞增殖及迁移。
基金Scientific Research Fund of the Institute of Pathogen Biology (2007IPB10)
文摘In light of the scarcity of reports on the interaction between HSV-1 nucleocapsid protein UL25 and its host cell proteins,the purpose of this study is to use yeast two-hybrid screening to search for cellular proteins that can interact with the UL25 protein.C9orf69,a protein of unknown function was identified.The interaction between the two proteins under physiological conditions was also confirmed by biological experiments including co-localization by fluorescence and immunoprecipitation.A preliminary study of the function of C9orf69 showed that it promotes viral proliferation.Further studies showed that C9orf69 did not influence viral multiplication efficiency by transcriptional regulation of viral genes,but indirectly promoted proliferation via interaction with UL25.
基金supported by the National Project on Major Infectious Diseases Prevention (Grant No. 2008ZX10002-009)the National Basic Research Program of China (Grant No. 2011CB910703)
文摘Viruses replicate and proliferate in host cells while continuously adjusting to and modulating the host environment.They encode a wide spectrum of multifunctional proteins,which interplay with and modify proteins in host cells.Viral genomes were chronologically the first to be sequenced.However,the corresponding viral proteomes,the alterations of host proteomes upon viral infection,and the dynamic nature of proteins,such as post-translational modifications,enzymatic cleavage,and activation or destruction by proteolysis,remain largely unknown.Emerging high-throughput techniques,in particular quantitative or semi-quantitative mass spectrometry-based proteomics analysis of viral and cellular proteomes,have been applied to define viruses and their interactions with their hosts.Here,we review the major areas of viral proteomics,including virion proteomics,structural proteomics,viral protein interactomics,and changes to the host cell proteome upon viral infection.
基金This research is supported by the Government of India, Ministry of Science and Technology, Mathematical Science Office, No. SR/S4/MS： 558/08 and supported partially by the National Natural Science Foundation of China （No. 11271314） and Plan for Scientific Innovation Talent of Henan Province （No. 144200510021）.
文摘In this research paper, our main objective is to find out the meticulous role of activated dendritic cells （DCs） during the human immunodeficiency virus （HIV） infection process. DCs play a dual role by enhancing both HIV infection progression, as well as antiviral immune response. To explore the implications of these dual roles, we have formulated our mathematical model and analyzed the model by both analytical and numerical approaches. By using an impulsive differential equation, we have studied the effect of DC-based vaccination. Analytically we have determined the threshold value of drug dosage and dosing interval for optimum levels of injection. We have also investigated the effect of perfect adherence of drug dose on the immune cell count in extreme cases and observed that, systematic drug dose of the immune cells leads to its maximum level.
