专利快速检索-快速检索全球专利，免费商用专利数据库-IPRDB

1. 发明申请

US20120189648A1 INFECTIOUS HEPATITIS C VIRUSES OF GENOTYPE 3A AND 4A AND USES THEREOF 有权
标题翻译：基因组3A和4A的感染性丙型肝炎病毒及其用途
公开(公告)号：US20120189648A1
公开(公告)日：2012-07-26
申请号：US13499663
申请日：2010-09-16
申请人： Judith M. Gottwein , Troels Kasper Hoyer Scheel , Robert Purcell , Jens Bukh
发明人： Judith M. Gottwein , Troels Kasper Hoyer Scheel , Robert Purcell , Jens Bukh
IPC分类号： A61K39/29 , C12N5/10 , C07K14/08 , A61P31/14 , C12Q1/70 , C07K16/10 , A61P37/04 , C12N15/40 , C12N7/00
CPC分类号： C12Q1/18 , C12N7/00 , C12N15/86 , C12N2770/24221 , C12N2770/24243 , C12Q1/707 , G01N33/5008
摘要： The present invention relates to molecular approaches to the production of nucleic acid sequences, which comprises the genome of infectious hepatitis C virus. In particular, invention provides nucleic acid sequences which comprise the genomes of infectious hepatitis C viruses of either genotype 3a (strain S52) or genotype 4a (strain ED43). The invention therefore relates to the use of the nucleic acid sequences and polypeptides encoded by all or part of the sequences in the development of vaccines and diagnostic assays for HCV and in the development of screening assays for the identification of antiviral agents for HCV. The invention therefore also relates to the use of viral particles derived from laboratory animals infected with S52 and ED43 viruses.
摘要翻译：本发明涉及生产核酸序列的分子方法，其包含感染性丙型肝炎病毒的基因组。特别地，本发明提供了包含基因型3a（菌株S52）或基因型4a（菌株ED43）的感染性丙型肝炎病毒的基因组的核酸序列。因此，本发明涉及由全部或部分序列编码的核酸序列和多肽在疫苗开发和HCV诊断测定中的用途，以及用于鉴定HCV抗病毒剂的筛选测定的开发。因此，本发明还涉及来自感染S52和ED43病毒的实验动物的病毒颗粒的用途。

2. 发明授权

US08946398B2 Infectious hepatitis C viruses of genotype 3A and 4A and uses thereof 有权
标题翻译：基因型3A和4A的感染性丙型肝炎病毒及其用途
公开(公告)号：US08946398B2
公开(公告)日：2015-02-03
申请号：US13499663
申请日：2010-09-16
申请人： Judith M. Gottwein , Troels Kasper Hoyer Scheel , Robert Purcell , Jens Bukh
发明人： Judith M. Gottwein , Troels Kasper Hoyer Scheel , Robert Purcell , Jens Bukh
IPC分类号： C07H21/04 , C07H21/02 , C12N7/00 , C12N15/86
CPC分类号： C12Q1/18 , C12N7/00 , C12N15/86 , C12N2770/24221 , C12N2770/24243 , C12Q1/707 , G01N33/5008
摘要： The present invention relates to molecular approaches to the production of nucleic acid sequences, which comprises the genome of infectious hepatitis C virus. In particular, invention provides nucleic acid sequences which comprise the genomes of infectious hepatitis C viruses of either genotype 3a (strain S52) or genotype 4a (strain ED43). The invention therefore relates to the use of the nucleic acid sequences and polypeptides encoded by all or part of the sequences in the development of vaccines and diagnostic assays for HCV and in the development of screening assays for the identification of antiviral agents for HCV. The invention therefore also relates to the use of viral particles derived from laboratory animals infected with S52 and ED43 viruses.
摘要翻译：本发明涉及生产核酸序列的分子方法，其包含感染性丙型肝炎病毒的基因组。特别地，本发明提供了包含基因型3a（菌株S52）或基因型4a（菌株ED43）的感染性丙型肝炎病毒的基因组的核酸序列。因此，本发明涉及由全部或部分序列编码的核酸序列和多肽在疫苗开发和HCV诊断测定中的用途，以及用于鉴定HCV抗病毒剂的筛选测定的开发。因此，本发明还涉及来自感染S52和ED43病毒的实验动物的病毒颗粒的用途。

3. 发明授权

US08846891B2 Infectious genotype 1a, 1b, 2a, 2b, 3a, 5a, 6a and 7a hepatitis C virus lacking the hypervariable region 1 (HVR1) 有权
标题翻译：传染性基因型1a，1b，2a，2b，3a，5a，6a和7a丙型肝炎病毒缺乏高变区1（HVR1）
公开(公告)号：US08846891B2
公开(公告)日：2014-09-30
申请号：US13060533
申请日：2009-08-07
申请人： Jannick Prento , Judith M. Gottwein , Troels Kasper Hoyer Scheel , Tanja Bertelsen Jensen , Jens Bukh
发明人： Jannick Prento , Judith M. Gottwein , Troels Kasper Hoyer Scheel , Tanja Bertelsen Jensen , Jens Bukh
IPC分类号： C12N7/00 , C12N5/10 , C12N15/51 , A61K39/29 , C07K14/005 , A61K39/00
CPC分类号： C12N7/00 , A61K39/12 , A61K39/29 , A61K2039/5254 , C07K14/005 , C12N2770/24222 , C12N2770/24234 , C12N2770/24261
摘要： The present inventors used the previously developed H77/JFH 1T27OOC,A4O8OT (1a/2a), J4/JFH 1T2996C,A4827T,ΔHVRI (1b/2a), J6/JFH 1ΔHVRI (2a/2a), J8/JFH 1ΔHVRI (2b/2a), S52/JFH 1T27i8G,τ7i6oc (3a/2a), SA13/JFH 1C34O5G,A3696G (5a/2a) and HK6a/JFH 1T1389c,A1590G (6a/2a) constructs for the deletion of Hypervariable Region 1 (HVR1) to construct viable, JFH 1 (genotype 2a) based, genomes. The present inventors serially passaged the viruses in cell culture obtaining relatively high HCV RNA titers and infectivity titers. Sequence analysis of the viruses identified mutations adapting H77/JFH 1T27OOC,A4O8OT,ΔHVR1 (1a/2a), J8/JFH 1ΔHVR1 (2b/2a), S52/JFH 1T2718G,T716OC,ΔHVR1 (3a/2a) and J4/JFH 1T2996C,A4827T,ΔHVR1 (1b/2a) to the HVR1 deletion.
摘要翻译：本发明人使用先前开发的H77 / JFH 1T27OOC，A4O8OT（1a / 2a），J4 / JFH 1T2996C，A4827T，＆Dgr; HVRI（1b / 2a），J6 / JFH1＆Dgr; HVRI（2a / 2a），J8 / 1 / Dgr; HVRI（2b / 2a），S52 / JFH 1T27i8G，τ7i6oc（3a / 2a），SA13 / JFH 1C34O5G，A3696G（5a / 2a）和HK6a / JFH 1T1389c，A1590G（6a / 2a）区域1（HVR1）构建可行的，基于基因型2a（基因型2a）的基因组。本发明人在细胞培养物中连续传代病毒获得相对高的HCV RNA滴度和感染滴度。病毒的序列分析鉴定了H77 / JFH 1T27OOC，A4O8OT，＆Dgr; HVR1（1a / 2a），J8 / JFH 1＆Dgr; HVR1（2b / 2a），S52 / JFH 1T2718G，T716OC和Dgr; HVR1（3a / 2a））和J4 / JFH 1T2996C，A4827T，＆Dgr; HVR1（1b / 2a）的HVR1缺失。

4. 发明申请

US20110059513A1 EFFICIENT CELL CULTURE SYSTEM FOR HEPATITIS C VIRUS GENOTYPE 1A AND 1B 有权
标题翻译：有效的细胞培养系统用于丙型肝炎病毒基因组1A和1B
公开(公告)号：US20110059513A1
公开(公告)日：2011-03-10
申请号：US12809345
申请日：2008-12-19
申请人： Troels Kasper Hoyer Scheel , Judith M. Gottwein , Jannick Prento , Tanja Bertelsen Jensen , Jens Bukh
发明人： Troels Kasper Hoyer Scheel , Judith M. Gottwein , Jannick Prento , Tanja Bertelsen Jensen , Jens Bukh
IPC分类号： C12N7/00 , C07H21/04
CPC分类号： C12N7/00 , A61K39/12 , A61K39/29 , A61K2039/525 , A61K2039/53 , C07K14/005 , C12N2770/24221 , C12N2770/24222 , C12N2770/24234
摘要： The present inventors developed hepatitis C virus 1a/2a and 1b/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and NS2 were replaced by the corresponding genes of the genotype Ia reference strain H77C or TN or the corresponding genes of the genotype Ib reference strain J4. Sequence analysis of recovered 1a/2a and 1b/2a recombinants from 2 serial passages and subsequent reverse genetic studies revealed adaptive mutations in e.g. p7, NS2 and/or NS3. In addition, the inventors demonstrate the possibility of using adaptive mutations identified for one HCV isolate in generating efficient cell culture systems for other isolates by transfer of mutations across isolates, subtypes or major genotypes. Furthermore neutralization studies showed that viruses of e.g. genotype 1 were efficiently neutralized by genotype Ia, 4a and 5a serum, an effect that could be utilized e.g. in vaccine development and immunological prophylaxis. The inventors in addition demonstrate the use of the developed systems for screening of antiviral substances in vitro and functional studies of the virus, e.g. identification of receptors required for HCV entry
摘要翻译：本发明人开发了丙型肝炎病毒1a / 2a和1b / 2a基因间重组体，其中JFH1结构基因（Core，E1和E2），p7和NS2被基因型1a参考菌株H77C或TN的相应基因替代，或基因型1b参考菌株J4的相应基因。来自2个连续传代和随后的反向遗传研究的回收的1a / 2a和1b / 2a重组体的序列分析揭示了例如， p7，NS2和/或NS3。此外，本发明人证明了通过在分离株，亚型或主要基因型上转移突变，可以使用为一种HCV分离株鉴定的适应性突变来产生用于其他分离物的有效细胞培养系统。此外，中和研究表明，基因型1被基因型1a，4a和5a血清有效地中和，可以使用例如，在疫苗开发和免疫预防中。本发明人另外证明了所开发的系统在体外筛选抗病毒物质的用途和病毒的功能研究，例如，鉴定HCV进入所需的受体

5. 发明授权

US08772022B2 Hepatitis C virus expressing reporter tagged NS5A protein 失效
标题翻译：丙型肝炎病毒表达报告基因标记NS5A蛋白
公开(公告)号：US08772022B2
公开(公告)日：2014-07-08
申请号：US13121565
申请日：2009-10-05
申请人： Judith M. Gottwein , Troels Kasper Hoyer Scheel , Jens Bukh , Jannick Prento , Tanja Bertelsen Jensen , Jacob Bo Lademann , Yiping Li
发明人： Judith M. Gottwein , Troels Kasper Hoyer Scheel , Jens Bukh , Jannick Prento , Tanja Bertelsen Jensen , Jacob Bo Lademann , Yiping Li
IPC分类号： C12N15/00 , C12N15/64 , C12N7/00 , C12N7/01 , C12N5/00 , A61K39/29
CPC分类号： C12N15/86 , A61K2039/525 , C07K14/005 , C12N7/00 , C12N2770/24222 , C12N2770/24243 , C12N2770/24251
摘要： Hepatitis C reporter viruses containing Core through NS2 of prototype isolates of all major HCV genotypes and the remaining genes of isolate JFH1, by insertion of reporter genes in domain III of HCV NS5A were developed. A deletion upstream of the inserted reporter gene sequence conferred favorable growth kinetics in Huh7.5 cells to these viruses. These reporter viruses can be used for high throughput analysis of drug and vaccine candidates as well as patient samples. JFH1-based intergenotypic recombinants with genotype specific homotypic 5′UTR, or heterotypic 5′UTR (either of genotype 1a (strain H77) or of genotype 3a (strain S52)) were also developed. The present inventors additionally developed J6/JFH1 recombinants with the 5′UTR of genotypes 1-6. These recombinants with different 5′UTRs are a useful to study the function of the 5′UTR in a genotype specific manner.
摘要翻译：开发了通过NS2的III型插入报告基因，通过NS2的核心通过NS2的所有主要HCV基因型的原型分离株和分离株JFH1的剩余基因的丙型肝炎报告病毒。插入报道基因序列上游的缺失在Huh7.5细胞中赋予这些病毒有利的生长动力学。这些报告病毒可用于药物和疫苗候选物以及患者样品的高通量分析。还开发了具有基因型特异性同种型5'UTR或异型5'UTR（基因型1a（菌株H77）或基因型3a（菌株S52））的基于JFH1的基因间重组体。本发明人还开发了具有基因型1-6的5'UTR的J6 / JFH1重组体。具有不同5'UTR的这些重组体可用于以基因型特异性方式研究5'UTR的功能。

6. 发明申请

US20100158948A1 ADAPTIVE MUTATIONS ALLOW ESTABLISHMENT OF JFH1-BASED CELL CULTURE SYSTEMS FOR HEPATITIS C VIRUS GENOTYPE 4A 有权
标题翻译：适应性突变允许建立基于JFH1的细胞培养系统，用于HEPATITIS C病毒基因组4A
公开(公告)号：US20100158948A1
公开(公告)日：2010-06-24
申请号：US12595825
申请日：2008-04-11
申请人： Troels Kasper Hoyer Scheel , Judith M. Gottwein , Jesper Eugen-Olsen , Jens Bukh
发明人： Troels Kasper Hoyer Scheel , Judith M. Gottwein , Jesper Eugen-Olsen , Jens Bukh
IPC分类号： C12N7/01 , C07H21/04 , C12N15/85 , C12N7/02 , C12Q1/70 , A61K31/7088 , A61P31/12
CPC分类号： C12N7/00 , A61K2039/5254 , C12N2770/24221
摘要： The present inventors developed three 4a/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and all of or part of NS2 were replaced by the corresponding genes of the genotype 4a reference strain ED43. The 4a/2a junction in NS2 was placed after the first transmembrane domain (a), in the cytoplasmic part (β) or at the NS2/NS3 cleavage site (y). Following transfection of Huh7.5 cells with RNA transcripts, infectious viruses were produced in the ED43/JFH1-β and -y cultures only. Compared to the 2a control virus, production of infectious viruses was significantly delayed. However, in subsequent passages efficient spread of infection and high HCV RNA titers were obtained. Infectivity titers were approximately 10-fold lower than for the 2a control virus. Sequence analysis of recovered 4a/2a recombinants from 3 serial passages and subsequent reverse genetic studies revealed a vital dependence on a mutation in the NS2 4a part. ED43/JFH1-γ further depended on a second NS2 mutation. Infectivity of the 4a/2a viruses was CD81 dependent. Conclusion: The developed 4a/2a viruses provide a robust in vitro tool for research in HCV genotype 4, including vaccine studies and functional analyses of an increasingly important genotype in the Middle East and Europe.
摘要翻译：本发明人开发了三种4a / 2a基因型重组体，其中JFH1结构基因（Core，E1和E2），p7以及NS2的全部或部分被基因型4a参考菌株ED43的相应基因替代。 NS2中的4a / 2a结合位于第一个跨膜结构域（a），细胞质部分（/ bgr）或NS2 / NS3切割位点（y）之后。在用RNA转录物转染Huh7.5细胞后，在ED43 / JFH1-＆bgr中产生感染性病毒; 和 - 只有文化。与2a对照病毒相比，感染性病毒的产生显着延迟。然而，在随后的传代中，获得了有效的感染传播和高HCV RNA滴度。感染滴度比2a对照病毒低约10倍。来自3个连续传代和随后的反向遗传研究的回收的4a / 2a重组体的序列分析揭示了对NS2a4部分突变的重要依赖性。 ED43 / JFH1-γ进一步依赖于第二NS2突变。 4a / 2a病毒的感染率依赖于CD81。结论：开发的4a / 2a病毒为HCV基因型4的研究提供了强大的体外工具，包括中东和欧洲越来越重要的基因型的疫苗研究和功能分析。

7. 发明授权

US08569472B2 Efficient cell culture system for hepatitis C virus genotype 6A 失效
标题翻译：丙型肝炎病毒基因型6A的高效细胞培养系统
公开(公告)号：US08569472B2
公开(公告)日：2013-10-29
申请号：US12808565
申请日：2008-12-19
申请人： Judith M. Gottwein , Troels Kasper Hoyer Scheel , Tanja Bertelsen Jensen , Jens Bukh
发明人： Judith M. Gottwein , Troels Kasper Hoyer Scheel , Tanja Bertelsen Jensen , Jens Bukh
IPC分类号： C07H21/00 , A61K39/12 , A61K39/29 , A61K39/295 , C12N7/00
CPC分类号： A61K39/29 , A61K39/12 , A61K2039/525 , A61K2039/53 , C07K14/005 , C12N7/00 , C12N2770/24221 , C12N2770/24222 , C12N2770/24234
摘要： The present inventors developed hepatitis C virus 6a/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 6a reference strain HK6a. Sequence analysis of recovered 6a/2a recombinants from 2 transfection experiments and subsequent reverse genetic studies revealed adaptive mutations in E1 and E2. Conclusion: The developed 6a/2a viruses provide a robust in vitro tool for research in HCV genotype 6, including vaccine studies and functional analysis.
摘要翻译：本发明人开发了丙型肝炎病毒6a / 2a基因型重组体，其中JFH1结构基因（Core，E1和E2），p7和完整的NS2被基因型6a参照菌株HK6a的相应基因替代。从2个转染实验和随后的反向遗传研究中回收的6a / 2a重组体的序列分析显示E1和E2中的适应性突变。结论：开发的6a / 2a病毒为HCV基因型6的研究提供了强大的体外工具，包括疫苗研究和功能分析。

8. 发明授权

US08506969B2 Efficient cell culture system for hepatitis C virus genotype 7a 失效
标题翻译：丙型肝炎病毒基因型7a高效细胞培养系统
公开(公告)号：US08506969B2
公开(公告)日：2013-08-13
申请号：US13059137
申请日：2009-07-31
申请人： Judith M. Gottwein , Troels Kasper Hoyer Scheel , Tanja Bertelsen Jensen , Jens Bukh
发明人： Judith M. Gottwein , Troels Kasper Hoyer Scheel , Tanja Bertelsen Jensen , Jens Bukh
IPC分类号： A61K39/12 , A61K39/29 , C12Q1/70 , C12N15/00 , C12N5/071 , C12N1/20
CPC分类号： C12N7/00 , A61K2039/525 , C07K14/005 , C07K2319/00 , C12N2770/24221 , C12N2770/24222
摘要： Genotype 7a has been identified recently, thus not much is known about the biology of this new, major HCV genotype. The present inventors developed hepatitis C virus 7a/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 7a strain QC69 and characterized them in Huh7.5 cells. Sequence analysis of 7a/JFH1 recombinants recovered after viral passage in Huh7.5 cells following 4 independent transfection experiments revealed adaptive mutations in Core, E2, NS2, NS5A and NS5B. In reverse genetic studies the importance of these mutations for improved growth kinetics was shown. Adapted 7a/JFH1 viruses showed growth kinetics, infectivity and RNA titers comparable to a previously developed 3a/JFH1 reference virus. Conclusion: The developed 7a/JFH1 viruses provide a robust in vitro tool for research in HCV genotype 7, including vaccine studies and functional analyses.
摘要翻译：最近鉴定了基因型7a，因此对这种新的主要HCV基因型的生物学知之甚少。本发明人开发了丙型肝炎病毒7a / 2a基因型重组体，其中JFH1结构基因（Core，E1和E2），p7和完整的NS2被基因型7a菌株QC69的相应基因替代，并在Huh7.5中表征细胞。在4次独立转染实验后Huh7.5细胞病毒传代后恢复的7a / JFH1重组体的序列分析显示核心，E2，NS2，NS5A和NS5B中的适应性突变。在反向遗传研究中，显示了这些突变对改善生长动力学的重要性。适应的7a / JFH1病毒显示与先前开发的3a / JFH1参考病毒相当的生长动力学，感染性和RNA滴度。结论：开发的7a / JFH1病毒为HCV基因型7研究提供了强大的体外工具，包括疫苗研究和功能分析。

9. 发明申请

US20120003719A1 INFECTIOUS GENOTYPE 1a, 1b, 2a, 2b, 3a, 5a, 6a and 7a HEPATITIS C VIRUS LACKING THE HYPERVARIABLE REGION 1 (HVR1) 有权
标题翻译：感染基因1a，1b，2a，2b，3a，5a，6a和7a HEPATITIS C VIRUS LACKING THE HYPERVARIABLE REGION 1（HVR1）
公开(公告)号：US20120003719A1
公开(公告)日：2012-01-05
申请号：US13060533
申请日：2009-08-07
申请人： Jannick Prento , Judith M. Gottwein , Troels Kasper Hoyer Scheel , Tanja Bertelsen Jensen , Jens Bukh
发明人： Jannick Prento , Judith M. Gottwein , Troels Kasper Hoyer Scheel , Tanja Bertelsen Jensen , Jens Bukh
IPC分类号： C12N7/00 , C12N5/10 , C12N15/51
CPC分类号： C12N7/00 , A61K39/12 , A61K39/29 , A61K2039/5254 , C07K14/005 , C12N2770/24222 , C12N2770/24234 , C12N2770/24261
摘要： The present inventors used the previously developed H77/JFH1T27OOC,A4O8OT (1a/2a), J4/JFH1T2996C,A4827T,ΔHVRI (1b/2a), J6/JFH1ΔHVRI (2a/2a), J8/JFH1ΔHVRI (2b/2a), S52/JFH1T27i8G,τ7i6oc (3a/2a), SA13/JFH1C34O5G,A3696G (5a/2a) and HK6a/JFH1T1389c,A1590G (6a/2a) constructs for the deletion of Hypervariable Region 1 (HVR1) to construct viable, JFH1 (geno-type 2a) based, genomes. The present inventors serially passaged the viruses in cell culture obtaining relatively high HCV RNA titers and infectivity titers. Sequence analysis of the viruses identified mutations adapting H77/JFH1T27OOC,A4O8OT,ΔHVR1 (1a/2a), J8/JFH1ΔHVR1 (2b/2a), S52/JFH1T2718G,T716OC,ΔHVR1 (3a/2a) and J4/JFH1T2996C,A4827T,ΔHVR1 (1b/2a) to the HVR1 deletion.
摘要翻译：本发明人使用先前开发的H77 / JFH1T27OOC，A4O8OT（1a / 2a），J4 / JFH1T2996C，A4827T，＆Dgr; HVRI（1b / 2a），J6 / JFH1＆Dgr; HVRI（2a / 2a），J8 / JFH1＆Dgr; HVRI 2b / 2a），S52 / JFH1T27i8G，τ7i6oc（3a / 2a），SA13 / JFH1C34O5G，A3696G（5a / 2a）和HK6a / JFH1T1389c，用于缺失高变区1（HVR1）构建的A1590G（6a / 2a）可行，基于JFH1（基因型2a）的基因组。本发明人在细胞培养物中连续传代病毒获得相对高的HCV RNA滴度和感染滴度。病毒的序列分析鉴定了H77 / JFH1T27OOC，A4O8OT，＆Dgr; HVR1（1a / 2a），J8 / JFH1和Dgr; HVR1（2b / 2a），S52 / JFH1T2718G，T716OC，＆Dgr; HVR1（3a / 2a）和J4 / JFH1T2996C，A4827T，＆Dgr; HVR1（1b / 2a）至HVR1缺失。

10. 发明申请

US20110294195A1 EFFICIENT CELL CULTURE SYSTEM FOR HEPATITIS C VIRUS GENOTYPE 7a 失效
标题翻译： HEPATITIS C病毒基因组的有效细胞培养系统7a
公开(公告)号：US20110294195A1
公开(公告)日：2011-12-01
申请号：US13059137
申请日：2009-07-31
申请人： Judith M. Gottwein , Troels Kasper Hoyer Scheel , Tanja Bertelsen Jensen , Jens Bukh
发明人： Judith M. Gottwein , Troels Kasper Hoyer Scheel , Tanja Bertelsen Jensen , Jens Bukh
IPC分类号： C12N7/00 , C12N5/10 , C07H21/04
CPC分类号： C12N7/00 , A61K2039/525 , C07K14/005 , C07K2319/00 , C12N2770/24221 , C12N2770/24222
摘要： Genotype 7a has been identified recently, thus not much is known about the biology of this new, major HCV genotype. The present inventors developed hepatitis C virus 7a/2a intergenotypic recombinants in which the JFH1 structural genes (Core, E1 and E2), p7 and the complete NS2 were replaced by the corresponding genes of the genotype 7a strain QC69 and characterized them in Huh7.5 cells. Sequence analysis of 7a/JFH1 recombinants recovered after viral passage in Huh7.5 cells following 4 independent transfection experiments revealed adaptive mutations in Core, E2, NS2, NS5A and NS5B. In reverse genetic studies the importance of these mutations for improved growth kinetics was shown. Adapted 7a/JFH1 viruses showed growth kinetics, infectivity and RNA titers comparable to a previously developed 3a/JFH1 reference virus. Conclusion: The developed 7a/JFH1 viruses provide a robust in vitro tool for research in HCV genotype 7, including vaccine studies and functional analyses.
摘要翻译：最近鉴定了基因型7a，因此对这种新的主要HCV基因型的生物学知之甚少。本发明人开发了丙型肝炎病毒7a / 2a基因型重组体，其中JFH1结构基因（Core，E1和E2），p7和完整的NS2被基因型7a菌株QC69的相应基因替代，并在Huh7.5中表征细胞。在4次独立转染实验后Huh7.5细胞病毒传代后恢复的7a / JFH1重组体的序列分析显示核心，E2，NS2，NS5A和NS5B中的适应性突变。在反向遗传研究中，显示了这些突变对改善生长动力学的重要性。适应的7a / JFH1病毒显示与先前开发的3a / JFH1参考病毒相当的生长动力学，感染性和RNA滴度。结论：开发的7a / JFH1病毒为HCV基因型7研究提供了强大的体外工具，包括疫苗研究和功能分析。

你已经成功收藏专利！

检索式保存成功!

IPRDB

热门服务

关于我们

友情链接

联系方式