Differential, type I interferon-mediated autophagic trafficking of hepatitis C virus proteins in mouse liver.
Differential, type I interferon-mediated autophagic trafficking of hepatitis C virus proteins in mouse liver.
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I型，I型干扰素介导的肝炎病毒蛋白在小鼠肝脏中的自噬运输。
DOI：
10.1053/j.gastro.2011.04.060
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发表时间：
2011-08
期刊：
影响因子：
29.4
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Desai MM;Gong B;Chan T;Davey RA;Soong L;Kolokoltsov AA;Sun J
丙型肝炎病毒丝氨酸蛋白酶NS3/4A可以裂解线粒体相关的抗病毒信号蛋白，阻断维甲酸诱导的基因I介导的干扰素反应。虽然这一机制被认为在丙型肝炎病毒介导的先天性免疫抑制中起着重要作用，但其在病毒持续存在中的意义尚不清楚。我们产生了在肝脏特异表达HCVNS3/4A蛋白的转基因小鼠，并用重组水泡性口炎病毒、合成的丙型肝炎病毒基因组、干扰素-α或干扰素-β攻击动物。我们评价了丙型肝炎病毒丝氨酸蛋白酶对先天免疫反应的影响及其相互作用。丙型肝炎病毒NS3/4A的表达导致肝内MAV的切割；用VSV或合成的丙型肝炎病毒基因组攻击转基因小鼠诱导了强烈的I型干扰素介导的应答，但并不显著低于对照组小鼠。不同的攻击剂诱导产生不同比例的干扰素-α和-β，导致内质网和线粒体相关病毒蛋白的自噬反应和囊泡运输模式不同。干扰素-β促进自溶酶体对病毒蛋白的降解。MAV的不同亚型与不同的I型干扰素介导的自噬反应有关；这些反应在将病毒成分运送到含有Toll样受体-3的内体间隔中发挥作用。干扰素-β-介导一种独特的抗病毒宿主防御的自噬机制。MAV在I型干扰素诱导的病毒蛋白自噬运输中起重要作用。
The hepatitis C virus (HCV) serine protease NS3/4A can cleave mitochondria-associated, anti-viral signaling protein (MAVS) and block retinoic acid-inducible gene I–mediated interferon (IFN) responses. Although this mechanism is thought to have an important role in HCV-mediated innate immunosuppression, its significance in viral persistence is not clear. We generated transgenic mice that express the HCV NS3/4A proteins specifically in the liver and challenged the animals with a recombinant vesicular stomatitis virus (VSV), a synthetic HCV genome, IFN-α, or IFN-β. We evaluated the effects of HCV serine protease on the innate immune responses and their interactions. Expression of HCV NS3/4A resulted in cleavage of intrahepatic MAVS; challenge of transgenic mice with VSV or a synthetic HCV genome induced strong, type I IFN-mediated responses that were not significantly lower than those of control mice. Different challenge agents induced production of different ratios of IFN-α and -β, resulting in different autophagic responses and vesicular trafficking patterns of endoplasmic reticulum- and mitochondria-associated viral proteins. IFN-β promoted degradation of the viral proteins by the autolysosome. Variant isoforms of MAVS were associated with distinct, type I IFN-mediated autophagic responses; these responses have a role in trafficking of viral components to endosomal compartments that contain toll-like receptor -3. IFN-β-mediates a distinct autophagic mechanism of anti-viral host defense. MAVS have an important role in type I IFN-induced autophagic trafficking of viral proteins.
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影响因子：
13.5
作者：
Beard, MR;Abell, G;Lemon, SM
通讯作者：
Lemon, SM
影响因子：
64.8
作者：
Meylan, E;Curran, J;Tschopp, R
通讯作者：
Tschopp, R
影响因子：
29.4
作者：
Honda, Masao;Sakai, Akito;Kaneko, Shuichi
通讯作者：
Kaneko, Shuichi
DOI：
10.1073/pnas.0408707102
发表时间：
2005-02-22
影响因子：
11.1
作者：
Foy, E;Li, K;Gale, M
通讯作者：
Gale, M
影响因子：
4.8
作者：
Korenaga, M;Wang, T;Weinman, SA
通讯作者：
Weinman, SA