PNAS：甲肝和丙肝病毒攻击同一个蛋白质
尽管都是感染肝脏，甲肝和丙肝病毒却极少有共同点。这两种病毒在遗传上间隔很远，传播途径不同并且导致很不同的疾病。甲肝通过摄入被感染患者的排泄颗粒（存在于受污染的食物、水等等）来传染，而丙肝则是主要通过直接接触被感染血液来传播。
此外，甲肝引发发烧、恶心和腹痛，但很少能导致死亡；丙肝则常常会经历数十年来破坏肝脏，到最后只有通过器官移植来拯救患者。
德克萨斯州大学Galveston医学分校的研究人员则认为这两种无关的肝脏病毒具有一个重要的相同点，就是避开免疫系统破坏的伎俩相同。两种病毒都通过攻击同一个蛋白来避过免疫攻击，而这个蛋白是引发抗病毒应答一个分子信号链中的关键连接点。
研究人员解释说，细胞中有大约30000种蛋白质，但是这两种几乎完全不同的病毒却选择工具同一个蛋白质。研究人员将这项研究的结果刊登在《PNAS》的在线版上。他们确定出这种蛋白质叫做MAVS，是一种线粒体抗病毒信号蛋白，对肝脏中任何病毒的存活至关重要。
MAVS蛋白质将少部分伸出线粒体外，当特化的受体分子检测到细胞中的病毒时，它们会停泊在MAVS蛋白上，引发一系列信号，最终导致β干扰素的产生。
今年的研究显示，丙肝能够产生一种叫做NS3/4A蛋白质，这种蛋白能够切割MAVS，进而干扰免疫信号并可能为病毒提供在肝脏中存活更长时间所需的保护。现在，Lemon和他的研究组证实了甲肝也可以利用另外一种叫做3ABC的蛋白质做同样的事情。
原始出处:
Published online before print April 16, 2007
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0611506104
Microbiology
Disruption of innate immunity due to mitochondrial targeting of a picornaviral protease precursor
( hepatitis virus | interferon regulatory factor 3 | interferon-beta | melanoma differentiation associated gene 5 | mitochondrial antiviral signaling protein )
, 
Center for Hepatitis Research, Institute for Human Infections and Immunity, Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555-1019
Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved March 12, 2007 (received for review December 22, 2006)
Mitochondrial antiviral signaling protein (MAVS) is an essential component of virus-activated signaling pathways that induce protective IFN responses. Its localization to the outer mitochondrial membrane suggests an important yet unexplained role for mitochondria in innate immunity. Here, we show that hepatitis A virus (HAV), a hepatotropic picornavirus, ablates type 1 IFN responses by targeting the 3ABC precursor of its 3Cpro cysteine protease to mitochondria where it colocalizes with and cleaves MAVS, thereby disrupting activation of IRF3 through the MDA5 pathway. The 3ABC cleavage of MAVS requires both the protease activity of 3Cpro and a transmembrane domain in 3A that directs 3ABC to mitochondria. Lacking this domain, mature 3Cpro protease is incapable of MAVS proteolysis. HAV thus disrupts host signaling by a mechanism that parallels that of the serine NS3/4A protease of hepatitis C virus, but differs in its use of a stable, catalytically active polyprotein processing intermediate. The unique requirement for mitochondrial localization of 3ABC underscores the importance of mitochondria to host control of virus infections within the liver.
更多原文链接： www.pnas.org/cgi/content/full/0611506104/DC1
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