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Quasispecies evolution in NS5A region of hepatitis C virus genotype 1b during interferon or combined interferon-ribavirin therapy

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World Journal of Gastroenterology 2007年第8期13卷 1195-1203页

作者： Pascal Veillon Christopher Payan hélène le guillou-guillemette Catherine Gaudy Franoise Lunel Laboratory of Virology Angers University Hospital 4 rue Larrey 49933 Angers cedex 9 France HIFIH Laboratory UPRES EA 3859 IFR 132 University of Angers rue de Haute Reculée 49045 Angers France Departement of Microbiology EA 3882 Brest University Hospital 2 avenue Foch 29609 Brest cedex France University Francois Rabelais INSERM ERI 19 Faculty of Medecine 10 Boulevard Tonnellé BP 3223 37032 Tours Cedex France

AIM: To evaluate the implication of substitutions in the hepatitis C virus (hCV) non-structural 5A (NS5A) protein in the resistance of hCV during mono-interferon (IFN) or combined IFN-ribavirin (IFN-R) therapy. Although NS5A has been reported to interact with the hCV RNA- dependent RNA polymerase, NS5B, as well as with many cellular proteins, the function of NS5A in the life cycle of hCV remains unclear. METhODS: hCV quasispecies were studied by clon- ing and sequencing of sequential isolates from patients infected by hCV genotype 1b. Patients were treated by IFN-α2b for 3 mo followed by IFN-α2b alone or com- bined IFN-R therapy for 9 additional months. Patients were categorized intro two groups based on their re- sponse to the treatments: 7 with sustained virological re- sponse (SVR) (quasispecies = 150) and 3 non-respond- ers (NR) to IFN-R (quasispecies = 106). RESULTS: Prior to treatment, SVR patients displayed a lower complexity of quasispecies than NR patients. Most patients had a decrease in the complexity of quasispe- cies during therapy. Analysis of amino acids substitu- tions showed that the degree of the complexity of the interferon sensitivity-determining region (ISDR) and the V3 domain of NS5A protein was able to discriminate thetwo groups of patients. Moreover, SVR patients displayed more variability in the NS5A region than NR patients. CONCLUSION: These results suggest that detailed mo- lecular analysis of the NS5A region may be important for understanding its function in IFN response during hCV 1b infection.

关键词： hepatitis C virus Quasispecies NS5A region Interferon sensitivity-determining region V3 domain

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Genetic diversity of the hepatitis C virus: Impact and issues inthe antiviral therapy

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World Journal of Gastroenterology 2007年第17期13卷 2416-2426页

作者： h le guillou-guillemette S Vallet C Gaudy-Graffin C Payan A Pivert A Goudeau F Lunel-Fabiani Laboratory of Virology University Hospital of Angers France and Laboratory HIFI UPRES EA 3859 University of Angers France Department of Microbiology EA 3882 CHU Morvan University Hospital of Brest France Université Francois Rabelais INSERM ERI 19 et CHRU de Tours Tours France

The hepatitis C Virus (hCV) presents a high degree of genetic variability which is explained by the combination of a lack of proof reading by the RNA dependant RNA polymerase and a high level of viral replication. The re- sulting genetic polymorphism defines a classification in clades, genotypes, subtypes, isolates and quasispecies. This diversity is known to reflect the range of responses to Interferon therapy. The genotype is one of the pre- dictive parameters currently used to define the antiviral treatment strategy and the chance of therapeutic suc- cess. Studies have also reported the potential impact of the viral genetic polymorphism in the outcome of antivi- ral therapy in patients infected by the same hCV geno- type. Both structural and non structural genomic regions of hCV have been suggested to be involved in the Inter- feron pathway and the resistance to antiviral therapy. In this review, we first detail the viral basis of hCV diversity. Then, the hCV genetic regions that may be implicated in resistance to therapy are described, with a focus on the structural region encoded by the E2 gene and the non- structural genes NS3, NS5A and NS5B. Both mechanisms of the Interferon resistance and of the new antiviral drugs are described in this review.

关键词： hepatitis C virus Genetic diversity Therapyresistance E2 NS3 NSSA NSSB

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具备瞬时抗皱性能的植物紧肤剂

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日用化学品科学 2018年第1期41卷 54-57页

作者： DAVID BOUDIER ANNE-ISABEL GUZMAN STRUILLOU ESTELle le DUDAL MIChEL DANA GERALDINE BON MAUD le guillou BRIGITTE CLOSS SILAB

通过3D分子结构的糖交联剂创新技术,INSTENSYL~?PX(INCI木薯淀粉)能迅速附着在皮肤表面并延展形成一层粘弹性膜,同时改善一系列皮肤参数。通过其对皮肤表面功效、感知效果以及处理时间和皮肤区域的测试,表明INSTENSYL~?PX具有快速紧肤功... 详细信息

通过3D分子结构的糖交联剂创新技术,INSTENSYL~?PX(INCI木薯淀粉)能迅速附着在皮肤表面并延展形成一层粘弹性膜,同时改善一系列皮肤参数。通过其对皮肤表面功效、感知效果以及处理时间和皮肤区域的测试,表明INSTENSYL~?PX具有快速紧肤功效,仅使用5min后即可体验,并能持续4h以上。同时,INSTENSYL~?PX还具有即时平滑和抗皱功效,无论对年轻还是成熟肌肤均适用。

关键词：植物紧肤剂瞬时效果平滑抗皱

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