盡管都是感染肝臟,，甲肝和丙肝病毒卻極少有共同點(diǎn),。這兩種病毒在遺傳上間隔很遠(yuǎn),，傳播途徑不同并且導(dǎo)致很不同的疾病,。甲肝通過攝入被感染患者的排泄顆粒（存在于受污染的食物、水等等）來傳染,，而丙肝則是主要通過直接接觸被感染血液來傳播,。
此外，甲肝引發(fā)發(fā)燒,、惡心和腹痛，但很少能導(dǎo)致死亡,；丙肝則常常會(huì)經(jīng)歷數(shù)十年來破壞肝臟,，到最后只有通過器官移植來拯救患者。
德克薩斯州大學(xué)Galveston醫(yī)學(xué)分校的研究人員則認(rèn)為這兩種無關(guān)的肝臟病毒具有一個(gè)重要的相同點(diǎn),，就是避開免疫系統(tǒng)破壞的伎倆相同,。兩種病毒都通過攻擊同一個(gè)蛋白來避過免疫攻擊，而這個(gè)蛋白是引發(fā)抗病毒應(yīng)答一個(gè)分子信號(hào)鏈中的關(guān)鍵連接點(diǎn),。
研究人員解釋說,，細(xì)胞中有大約30000種蛋白質(zhì)，但是這兩種幾乎完全不同的病毒卻選擇工具同一個(gè)蛋白質(zhì),。研究人員將這項(xiàng)研究的結(jié)果刊登在《PNAS》的在線版上,。他們確定出這種蛋白質(zhì)叫做MAVS，是一種線粒體抗病毒信號(hào)蛋白,，對(duì)肝臟中任何病毒的存活至關(guān)重要,。
MAVS蛋白質(zhì)將少部分伸出線粒體外，當(dāng)特化的受體分子檢測(cè)到細(xì)胞中的病毒時(shí),，它們會(huì)停泊在MAVS蛋白上,，引發(fā)一系列信號(hào)，最終導(dǎo)致β干擾素的產(chǎn)生,。
今年的研究顯示,，丙肝能夠產(chǎn)生一種叫做NS3/4A蛋白質(zhì)，這種蛋白能夠切割MAVS,，進(jìn)而干擾免疫信號(hào)并可能為病毒提供在肝臟中存活更長(zhǎng)時(shí)間所需的保護(hù)?，F(xiàn)在，Lemon和他的研究組證實(shí)了甲肝也可以利用另外一種叫做3ABC的蛋白質(zhì)做同樣的事情,。
原始出處:
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 )
Yan Yang , Yuqiong Liang, Lin Qu, Zeming Chen, MinKyung Yi, Kui Li, and Stanley M. Lemon
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.
