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    NOVEL VIRUSES FOUND IN RATTUS NORVEGICUS AND USES THEREOF
    2.
    发明申请
    NOVEL VIRUSES FOUND IN RATTUS NORVEGICUS AND USES THEREOF 审中-公开
    在新西兰北部发现的新病毒及其用途

    公开(公告)号：WO2016061210A2

    公开(公告)日：2016-04-21

    申请号：PCT/US2015/055510

    申请日：2015-10-14

    申请人： THE TRUSTEES OF COLUMBIA UNIVERSITY IN THE CITY OF NEW YORK

    发明人： LIPKIN, W., Ian ,  KAPOOR, Amit ,  BHAT, Meera ,  FIRTH, Cadhla ,  QUAN, Phenix-Lan

    IPC分类号： A61K48/00 ,  C12Q1/70

    CPC分类号： C12N7/00 ,  C07K14/005 ,  C12N2770/24221 ,  C12N2770/24222 ,  C12Q1/701

    摘要： The invention is directed to novel hepatotropic hepaciviruses isolated in Norway rats (Rattus norvegicus), designated NrHV-1 or RHV-rn-NY01 and NrHV-2 or RHV-rn-NY02, and isolated nucleic acids sequences and polypeptides thereof. The invention also relates to antibodies against antigens from NrHV- 1 or NrHV-2 found in Rattus norvegicus. The invention also relates to iRNAs which target nucleic acid sequences of NrHV- 1 or NrHV-2 found in Rattus norvegicus. The invention is related to methods for detecting the presence or absence of NrHV-1 or NrHV-2 found in Rattus norvegicus in an animal. The invention is also related to immunogenic compositions for inducing an immune response against NrHV-1 or NrHV-2 in an animal. The invention is also related to a cell culture system and a laboratory animal to model human hepatitis C virus (HCV).

    摘要翻译： 本发明涉及在挪威大鼠（Rattus norvegicus）中分离的命名为NrHV-1或RHV-rn-NY01和NrHV-2或RHV-rn-NY02的新型肝致肝炎病毒，以及分离的核酸序列及其多肽。 本发明还涉及针对来自Rattus norvegicus的NrHV-1或NrHV-2抗原的抗体。 本发明还涉及靶向Rattus norvegicus中发现的NrHV-1或NrHV-2的核酸序列的iRNA。 本发明涉及用于检测在动物体内发现的黑曲霉中存在或不存在NrHV-1或NrHV-2的方法。 本发明还涉及用于在动物中诱导针对NrHV-1或NrHV-2的免疫应答的免疫原性组合物。 本发明还涉及细胞培养系统和用于模拟人丙型肝炎病毒（HCV）的实验室动物。

    EFFICIENT CELL CULTURE SYSTEM FOR HEPATITIS C VIRUS GENOTYPE 7a
    5.
    发明申请
    EFFICIENT CELL CULTURE SYSTEM FOR HEPATITIS C VIRUS GENOTYPE 7a 审中-公开
    HEPATITIS C病毒基因组的有效细胞培养系统7a

    公开(公告)号：WO2010017819A1

    公开(公告)日：2010-02-18

    申请号：PCT/DK2009/050193

    申请日：2009-07-31

    申请人： Hvidovre Hospital ,  GOTTWEIN, Judith M. ,  SCHEEL, Troels Kasper Høyer ,  JENSEN, Tanja Bertelsen ,  BUKH, Jens

    发明人： GOTTWEIN, Judith M. ,  SCHEEL, Troels Kasper Høyer ,  JENSEN, Tanja Bertelsen ,  BUKH, Jens

    IPC分类号： C12N15/51 ,  C12N15/62 ,  C12N7/00 ,  C07K14/18 ,  A61K39/29 ,  C07K16/10

    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。 在反向遗传学研究中显示出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 / JFH1参照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的研究提供了强大的体外工具，包括疫苗研究和功能分析。

    ADAPTIVE MUTATIONS ALLOW ESTABLISHMENT OF JFH1-BASED CELL CULTURE SYSTEMS FOR HEPATITIS C VIRUS GENOTYPE 4A
    8.
    发明申请
    ADAPTIVE MUTATIONS ALLOW ESTABLISHMENT OF JFH1-BASED CELL CULTURE SYSTEMS FOR HEPATITIS C VIRUS GENOTYPE 4A 审中-公开
    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：WO2008125119A1

    公开(公告)日：2008-10-23

    申请号：PCT/DK2008/050085

    申请日：2008-04-11

    申请人： HVIDOVRE HOSPITAL ,  SCHEEL, Troels Kasper Høyer ,  GOTTWEIN, Judith M. ,  EUGEN-OLSEN, Jesper ,  BUKH, Jens

    发明人： SCHEEL, Troels Kasper Høyer ,  GOTTWEIN, Judith M. ,  EUGEN-OLSEN, Jesper ,  BUKH, Jens

    IPC分类号： C12N7/00 ,  C12N7/02 ,  C12N15/51 ,  C12N5/10 ,  C07K14/18 ,  A61K39/29

    CPC分类号： C12N7/00 ,  A61K2039/5254 ,  C12N2770/24221

    摘要： The present inventors developed three 4a/2a intergenotypic recombinants in which the JFHl structural genes (Core, El 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 (α), 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/JFHl-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/JFHl-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连接处置于第一跨膜结构域（a），细胞质部分（ß）或NS2 / NS3切割位点（y）之后。 在用RNA转录物转染Huh7.5细胞后，仅在ED43 / JFH1-β和-y培养物中产生感染性病毒。 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 / JFHl-？ 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。

    HEPATITIS C VIRUS REPLICATION SYSTEM
    9.
    发明申请
    HEPATITIS C VIRUS REPLICATION SYSTEM 审中-公开
    HEPATITIS C病毒复制系统

    公开(公告)号：WO2006038129A3

    公开(公告)日：2006-06-22

    申请号：PCT/IB2005003957

    申请日：2005-10-03

    申请人： CHIRON SRL ,  MEROLA MARCELLO

    发明人： MEROLA MARCELLO

    IPC分类号： C07K14/18 ,  A61K38/00 ,  A61K39/29 ,  C12N5/10

    CPC分类号： C07K14/005 ,  A61K38/00 ,  A61K2039/5258 ,  C12N7/00 ,  C12N2770/24221 ,  C12N2770/24222 ,  C12N2770/24252

    摘要： A cell including: (a) a hepatitis C virus genome, and/or nucleic acid encoding a hepatitis C virus genome; and (b) nucleic acid encoding one or both of hepatitis C virus proteins El and E2. The cells can be grown in culture in order to support HCV replication, and HCV virions can be purified from them.

    摘要翻译： 一种细胞，包括：（a）丙型肝炎病毒基因组和/或编码丙型肝炎病毒基因组的核酸; 和（b）编码丙型肝炎病毒蛋白E1和E2之一或两者的核酸。 细胞可以在培养物中生长以支持HCV复制，并且可以从其中纯化HCV病毒粒子。

    HEPATITIS C VIRUS REPLICATION SYSTEM
    10.
    发明申请
    HEPATITIS C VIRUS REPLICATION SYSTEM 审中-公开
    丙型肝炎病毒复制系统

    公开(公告)号：WO2006038129A2

    公开(公告)日：2006-04-13

    申请号：PCT/IB2005/003957

    申请日：2005-10-03

    申请人： CHIRON SRL ,  MEROLA, Marcello

    发明人： MEROLA, Marcello

    CPC分类号： C07K14/005 ,  A61K38/00 ,  A61K2039/5258 ,  C12N7/00 ,  C12N2770/24221 ,  C12N2770/24222 ,  C12N2770/24252

    摘要： A cell including: (a) a hepatitis C virus genome, and/or nucleic acid encoding a hepatitis C virus genome; and (b) nucleic acid encoding one or both of hepatitis C virus proteins El and E2. The cells can be grown in culture in order to support HCV replication, and HCV virions can be purified from them.

    摘要翻译： 一种细胞，其包含：（a）丙型肝炎病毒基因组，和/或编码丙型肝炎病毒基因组的核酸; 和（b）编码丙型肝炎病毒蛋白E1和E2之一或两者的核酸。 细胞可以在培养物中生长以支持HCV复制，并且可以从它们纯化HCV病毒体。