CD59 incorporation protects hepatitis C virus against complement-mediated destruction.
CD59 incorporation protects hepatitis C virus against complement-mediated destruction.
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CD59掺入可保护丙型肝炎病毒免受补体介导的破坏。
DOI：
10.1002/hep.24686
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发表时间：
2012-02
期刊：
影响因子：
13.5
通讯作者：
Yu, Qigui
中科院分区：
文献类型：
--
作者：
Amet, Tohti;Ghabril, Marwan;Chalasani, Naga;Byrd, Daniel;Hu, Ningjie;Grantham, Ayslinn;Liu, Ziqing;Qin, Xuebin;He, Johnny J.;Yu, Qigui
已经发现包括HIV-1、CMV、HSV-1、埃博拉病毒、牛痘病毒和流感病毒在内的几种包膜病毒将补体激活的宿主调节因子（RCA）掺入其病毒包膜中，并因此逃避抗体依赖性补体介导的裂解（ADCML）。HCV是黄病毒科的有包膜病毒，并掺入10种以上的宿主脂蛋白。慢性感染HCV的患者产生高滴度和交叉反应性中和抗体（nAb），但未能清除病毒，这增加了HCV也可能使用类似的RCA掺入策略来逃避ADCML的可能性。因此，目前的研究进行，以确定是否HCV病毒粒子纳入生物功能的CD 59，RCA的关键成员。我们的实验提供了几条证据，证明CD 59与来自Huh7.5.1细胞或HCV感染患者血浆样品的HCV颗粒的外膜相关。首先，HCV颗粒被CD 59特异性抗体捕获。其次，通过免疫印迹分析在纯化的HCV颗粒中检测到CD 59，并且通过ELISA在HCV感染的Huh7.5.1细胞的无细胞上清液中检测到CD 59，但未感染或Ad 5（无包膜细胞溶解病毒）感染的Huh7.5.1细胞中未检测到CD 59。最后，用其阻断剂废除CD 59功能增加了HCV病毒体对ADCML的敏感性，导致HCV感染性显著降低。此外，直接添加CD 59阻断剂到HCV感染患者的血浆样品中增加了自体病毒溶解。我们的研究第一次证明了CD 59以保护免于ADCML的水平掺入细胞系衍生的和血浆原代HCV病毒体中。这也是第一份报告表明，直接加入RCA阻断剂到血浆中HCV感染的患者，使内源性血浆病毒粒子对ADCML敏感。
Several enveloped viruses including HIV-1, CMV, HSV-1, Ebola virus, vaccinia virus, and influenza virus have been found to incorporate host regulators of complement activation (RCA) into their viral envelopes and, as a result, escape antibody-dependent complement-mediated lysis (ADCML). HCV is an enveloped virus of the family Flaviviridae and incorporates more than 10 host lipoproteins. Patients chronically infected with HCV develop high-titer and cross-reactive neutralizing antibodies (nAbs) yet fail to clear the virus, raising the possibility that HCV may also use the similar strategy of RCA incorporation to escape ADCML. The current study was therefore undertaken to determine whether HCV virions incorporate biologically functional CD59, a key member of RCA. Our experiments provided several lines of evidence demonstrating that CD59 was associated with the external membrane of HCV particles derived from either Huh7.5.1 cells or plasma samples from HCV-infected patients. First, HCV particles were captured by CD59-specific Abs. Second, CD59 was detected in purified HCV particles by immunoblot analysis and in the cell-free supernatant from HCV-infected Huh7.5.1 cells, but not from uninfected or Ad5 (a nonenveloped cytolytic virus)-infected Huh7.5.1 cells by ELISA. Last, abrogation of CD59 function with its blockers increased the sensitivity of HCV virions to ADCML, resulting in a significant reduction of HCV infectivity. Additionally, direct addition of CD59 blockers into plasma samples from HCV-infected patients increased autologous virolysis. our study, for the first time, demonstrates that CD59 is incorporated into both cell line-derived and plasma primary HCV virions at levels that protect against ADCML. This is also the first report to show that direct addition of RCA blockers into plasma from HCV-infected patients renders endogenous plasma virions sensitive to ADCML.
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影响因子：
14.8
作者：
Sakamoto, H;Okamoto, K;Sudoh, M
通讯作者：
Sudoh, M
DOI：
10.1073/pnas.2335981100
发表时间：
2003-11-25
影响因子：
11.1
作者：
Bartosch, B;Bukh, J;Purcell, RH
通讯作者：
Purcell, RH
影响因子：
11.8
作者：
Netski, DM;Mosbruger, T;Cox, A
通讯作者：
Cox, A
影响因子：
3.8
作者：
Chuang, Wing Chia-Ming;Allain, Jean-Pierre
通讯作者：
Allain, Jean-Pierre
影响因子：
4.8
作者：
Merz, Andreas;Long, Gang;Bartenschlager, Ralf
通讯作者：
Bartenschlager, Ralf