Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody.
Clearance of persistent hepatitis C virus infection in humanized mice using a claudin-1-targeting monoclonal antibody.
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使用Claudin-1靶向单克隆抗体的人源化小鼠中持续性丙型肝炎病毒感染的清除。
DOI：
10.1038/nbt.3179
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发表时间：
2015-05
影响因子：
46.9
通讯作者：
Baumert, Thomas F.
中科院分区：
文献类型：
--
作者：
Mailly, Laurent;Xiao, Fei;Lupberger, Joachim;Wilson, Garrick K.;Aubert, Philippe;Duong, Franois H. T.;Calabrese, Diego;Leboeuf, Celine;Fofana, Isabel;Thumann, Christine;Bandiera, Simonetta;Luergehetmann, Marc;Volz, Tassilo;Davis, Christopher;Harris, Helen J.;Mee, Christopher J.;Girardi, Erika;Chane-Woon-Ming, Beatrice;Ericsson, Maria;Fletcher, Nicola;Bartenschlager, Ralf;Pessaux, Patrick;Vercauteren, Koen;Meuleman, Philip;Villa, Pascal;Kaderali, Lars;Pfeffer, Sebastien;Heim, Markus H.;Neunlist, Michel;Zeisel, Mirjam B.;Dandri, Maura;McKeating, Jane A.;Robinet, Eric;Baumert, Thomas F.
丙型肝炎病毒（HCV）感染是导致肝硬化和癌症的主要原因。HCV和其他病原体的细胞进入是由紧密连接蛋白（TJ）介导的，但TJ蛋白的成功靶向治疗尚未有报道。利用人肝嵌合小鼠模型，我们发现TJ蛋白claudin-1特异性单克隆抗体可消除慢性HCV感染而无可检测的毒性。该抗体抑制HCV进入、细胞间传播和病毒诱导的信号事件。抗体治疗减少了体内感染hcv的肝细胞数量，强调了通过宿主进入因子重新感染以维持慢性感染的必要性。总之，我们证明了一种靶向病毒受体的抗体可以治愈慢性病毒感染，并揭示了TJ蛋白作为抗病毒治疗的靶点。
Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and cancer. Cell entry of HCV and other pathogens is mediated by tight junction (TJ) proteins, but successful therapeutic targeting of TJ proteins has not been reported yet. Using a human liver-chimeric mouse model we show that a monoclonal antibody specific for TJ protein claudin-1 eliminates chronic HCV infection without detectable toxicity. This antibody inhibits HCV entry, cell-cell transmission and virus-induced signaling events. Antibody treatment reduces the number of HCV-infected hepatocytes in vivo, highlighting the need for de novo infection via host entry factors to maintain chronic infection. In summary, we demonstrate that an antibody targeting a virus receptor can cure chronic viral infection and uncover TJ proteins as targets for antiviral therapy.
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影响因子：
13.5
作者：
Fletcher, Nicola F.;Sutaria, Rupesh;Jo, Juandy;Barnes, Amy;Blahova, Miroslava;Meredith, Luke W.;Cosset, Francois-Loic;Curbishley, Stuart M.;Adams, David H.;Bertoletti, Antonio;McKeating, Jane A.
通讯作者：
McKeating, Jane A.
影响因子：
13.5
作者：
Meuleman, Philip;Catanese, Maria Teresa;Nicosia, Alfredo
通讯作者：
Nicosia, Alfredo
DOI：
10.1073/pnas.0504877103
发表时间：
2006-05-09
影响因子：
11.1
作者：
Pietschmann, Thomas;Kaul, Artur;Bartenschlager, Ralf
通讯作者：
Bartenschlager, Ralf
影响因子：
4.4
作者：
Lan, Lin;Gorke, Sebastian;Baumert, Thomas F.
通讯作者：
Baumert, Thomas F.
影响因子：
82.9
作者：
Law, Mansun;Maruyama, Toshiaki;Burton, Dennis R.
通讯作者：
Burton, Dennis R.