Complement lysis activity in autologous plasma is associated with lower viral loads during the acute phase of HIV-1 infection.
Complement lysis activity in autologous plasma is associated with lower viral loads during the acute phase of HIV-1 infection.
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DOI：
10.1371/journal.pmed.0030441
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发表时间：
2006-11
期刊：
影响因子：
15.8
通讯作者：
Trkola, Alexandra
中科院分区：
文献类型：
--
作者：
Huber, Michael;Fischer, Marek;Misselwitz, Benjamin;Manrique, Amapola;Kuster, Herbert;Niederoest, Barbara;Weber, Rainer;von Wyl, Viktor;Guenthard, Huldrych F.;Trkola, Alexandra
为探究抗体介导的补体裂解有助于控制HIV - 1感染中的病毒血症这一可能性，我们测量了患者血浆介导自体原发病毒补体裂解的活性。
本研究使用了两组患者的血清，一组是25名急性HIV - 1感染患者，另一组是31名慢性感染患者。我们开发了一种基于实时PCR的新型检测策略，能够可靠且灵敏地定量检测补体对病毒的裂解作用。在大多数患者中，病毒分离时获取的血浆可诱导对自体病毒分离株的补体裂解。在慢性疾病阶段，针对自体病毒和异源原发病毒株JR - FL的总体裂解活性高于急性期。最显著的是，我们发现急性期（而非慢性感染期）的血浆病毒载量水平与自体补体裂解活性呈负相关。针对包膜（Env）蛋白gp120和gp41的抗体反应性与针对JR - FL的裂解活性呈正相关，表明抗Env反应介导了补体裂解。针对自体病毒的中和作用与补体裂解活性无关，这表明补体裂解主要由非中和抗体引起。
总体而言，我们的数据提供了证据，表明抗体介导的补体对病毒粒子的裂解在感染过程中迅速发生且在早期就有效；因此，它应被视为一个与其他免疫功能协同控制体内病毒血症的参数。
HIV病毒粒子的抗体介导的补体裂解在HIV感染过程中迅速发生且在早期就有效。
如果不进行治疗，大多数感染人类免疫缺陷病毒（HIV）的人最终会发展为获得性免疫缺陷综合征（AIDS）。随着时间的推移，HIV感染并杀死他们的CD4 T淋巴细胞——免疫系统中刺激B淋巴细胞产生抗体（识别和消灭病原体的蛋白质）并帮助CD8 T淋巴细胞杀死含有病毒和细菌的细胞的细胞。CD4 T淋巴细胞的缺失——“适应性免疫”的核心参与者——使患者极易受到感染。然而，免疫系统并不会坐以待毙。它会通过产生细胞介导的免疫反应来尽力对抗HIV感染，在这种反应中T淋巴细胞攻击HIV感染的细胞。它还会产生“体液”免疫反应，即产生识别HIV的抗体。其中一些是中和抗体，可阻止HIV进入其宿主细胞并进行复制。其他抗体可能通过诱导病毒的破坏来限制病毒的传播。它们做到这一点的一种方式是激活免疫系统的另一部分——补体系统，该系统可以打开并杀死病毒（这被称为抗体介导的补体裂解）。此外，抗体和补体可以包裹HIV病毒颗粒，以便吞噬细胞（例如巨噬细胞——另一种免疫系统细胞）吞噬并消灭病毒。
体液免疫在对抗HIV感染中所起的作用复杂且鲜为人知。特别是，尚不清楚补体系统是有助于阻止HIV的传播，还是会因促进其进入宿主细胞而无意中帮助其传播。尽可能多地了解对HIV感染的体液免疫反应非常重要，这样才能设计出对HIV提供最大保护的疫苗。在这项研究中，研究人员调查了抗体介导的补体裂解是否能控制HIV感染患者血液中的病毒量。
研究人员从近期感染HIV（急性感染）的患者和感染一段时间（慢性感染）的患者那里收集血浆（血液中含有循环抗体的液体部分）。他们还从每位患者中分离出HIV——即所谓的自体病毒。然后，他们使用一种灵敏的分子生物学检测方法，在提供来自健康供体的补体的情况下，测试每个血浆样本裂解自体病毒（以及一种标准病毒）的能力。大多数血浆样本能够裂解HIV，尽管从慢性感染患者采集的样本通常比从急性感染患者采集的样本引起更多的裂解。在慢性感染患者中，诱导的裂解水平与患者血液中的病毒量（病毒血症）无关。然而，从病毒载量较高的急性感染患者采集的血浆在裂解检测中的活性低于从病毒载量较低的患者采集的血浆。最后，研究人员表明，各种血浆样本中针对HIV的两种包膜蛋白的抗体水平与每个样本裂解标准病毒的能力密切相关，并且这些抗体主要是非中和抗体。
通过表明在实验室中HIV的抗体介导的补体裂解在急性感染期间与患者的病毒载量呈负相关，这些发现表明（但未证明）HIV的抗体介导的补体裂解有助于在HIV感染早期控制病毒血症。但是，这种形式的体液免疫在对抗HIV感染中的重要性仍然不确定，因为补体有可能促进也有可能阻止病毒传播。需要进一步的研究来阐明这些影响在患者中哪种占主导地位，并充分表征激活补体的抗体。尽管如此，这项研究的结果表明，在未来设计有效的HIV疫苗时应考虑激活补体的抗体。
请通过本摘要的在线版本访问这些网站：http://dx.doi.org/10.1371/journal.pmed.0030441
美国国家过敏和传染病研究所关于HIV感染和AIDS的情况说明书
美国卫生与公众服务部关于AIDS的信息，包括疫苗信息
美国疾病控制与预防中心关于HIV/AIDS的信息
Aidsmap（由慈善机构NAM提供的关于HIV和免疫系统的信息）
维基百科关于补体系统的页面（注：维基百科是一个任何人都可以编辑的免费在线百科全书）
To explore the possibility that antibody-mediated complement lysis contributes to viremia control in HIV-1 infection, we measured the activity of patient plasma in mediating complement lysis of autologous primary virus. Sera from two groups of patients—25 with acute HIV-1 infection and 31 with chronic infection—were used in this study. We developed a novel real-time PCR-based assay strategy that allows reliable and sensitive quantification of virus lysis by complement. Plasma derived at the time of virus isolation induced complement lysis of the autologous virus isolate in the majority of patients. Overall lysis activity against the autologous virus and the heterologous primary virus strain JR-FL was higher at chronic disease stages than during the acute phase. Most strikingly, we found that plasma virus load levels during the acute but not the chronic infection phase correlated inversely with the autologous complement lysis activity. Antibody reactivity to the envelope (Env) proteins gp120 and gp41 were positively correlated with the lysis activity against JR-FL, indicating that anti-Env responses mediated complement lysis. Neutralization and complement lysis activity against autologous viruses were not associated, suggesting that complement lysis is predominantly caused by non-neutralizing antibodies. Collectively our data provide evidence that antibody-mediated complement virion lysis develops rapidly and is effective early in the course of infection; thus it should be considered a parameter that, in concert with other immune functions, steers viremia control in vivo. Antibody-mediated complement lysis of HIV virions develops rapidly and is effective already early in the course of HIV infection. If untreated, most people who become infected with the human immunodeficiency virus (HIV) eventually develop acquired immunodeficiency syndrome (AIDS). Over time, HIV infects and kills their CD4 T lymphocytes—immune system cells that stimulate B lymphocytes to make antibodies (proteins that recognize and destroy infectious agents) and that help CD8 T lymphocytes to kill cells that contain viruses and bacteria. The loss of CD4 T lymphocytes—a central player in “adaptive immunity”—leaves patients very susceptible to infections. However, the immune system does not die quietly. It does its best to fight HIV infection by mounting a cell-mediated immune response in which T lymphocytes attack HIV-infected cells. It also mounts a “humoral” immune response in which antibodies that recognize HIV are made. Some of these are neutralizing antibodies, which prevent HIV entering its host cells and replicating. Other antibodies may limit viral spread by inducing destruction of the virus. One way they can do this is by activating another part of the immune system called the complement system, which can break open and kill viruses (this is known as antibody-mediated complement lysis). In addition, antibodies and complement can coat the HIV virus particles so that phagocytes (for instance macrophages—yet another type of immune system cell) engulf and destroy the virus. The role that humoral immunity plays in fighting HIV infection is complex and poorly understood. In particular, it is not clear whether the complement system helps to stop the spread of HIV or whether it inadvertently helps it to spread by facilitating its entry into host cells. It is important to understand as much as possible about the humoral immune response to HIV infection so that vaccines can be designed to provide maximum protection against HIV. In this study, the researchers have investigated whether antibody-mediated complement lysis controls the amount of virus in the blood of patients infected with HIV. The researchers collected plasma (the liquid part of blood that contains circulating antibodies) from patients recently infected with HIV (acute infection) and patients who had been infected for some time (chronically infected). They also isolated HIV from each of the patients—so-called autologous virus. They then used a sensitive molecular biology assay to test each plasma sample for its ability to lyse the autologous virus (and also a standard virus) when supplied with complement from a healthy donor. Most of the plasma samples were able to lyse HIV, although the samples taken from chronically infected patients generally caused more lysis than those from acutely infected patients. In the chronically infected patients, the level of lysis induced was not related to the amount of virus in the patients' blood (viremia). However, plasma taken from acutely infected patients with higher viral loads was less active in the lysis assay than plasma taken from patients with lower viral loads. Finally, the researchers showed that the levels of antibodies in the various plasma samples to the two envelope proteins of HIV correlated strongly with the ability of each sample to lyse the standard virus and that these antibodies were mainly non-neutralizing antibodies. By showing that antibody-mediated complement lysis of HIV in the laboratory is inversely related to the patients' viral loads during acute infection, these findings suggest (but do not prove) that antibody-mediated complement lysis of HIV contributes to the control of viremia early in HIV infections. But, the importance of this form of humoral immunity in combating HIV infections remains uncertain, since complement has the potential to enhance as well as block viral spread. Further work is needed to unravel which of these effects is dominant in patients and to characterize fully the antibodies that activate complement. Nevertheless, the results of this study suggest that complement-activating antibodies should be considered in future attempts to design an effective HIV vaccine. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030441. National Institute of Allergy and Infectious Diseases fact sheet on HIV infection and AIDS US Department of Health and Human Services information on AIDS, including information on vaccines US Centers for Disease Control and Prevention information on HIV/AIDS Aidsmap information on HIV and the immune system provided by the charity NAM Wikipedia pages on the complement system (note: Wikipedia is a free online encyclopedia that anyone can edit)
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影响因子：
15.8
作者：
Kaufmann DE;Lichterfeld M;Altfeld M;Addo MM;Johnston MN;Lee PK;Wagner BS;Kalife ET;Strick D;Rosenberg ES;Walker BD
通讯作者：
Walker BD
DOI：
10.1084/jem.192.5.637
发表时间：
2000-09-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Moir S;Malaspina A;Li Y;Chun TW;Lowe T;Adelsberger J;Baseler M;Ehler LA;Liu S;Davey RT Jr;Mican JA;Fauci AS
通讯作者：
Fauci AS
影响因子：
6.4
作者：
BELEC, L;DUPRE, T;PILLOT, J
通讯作者：
PILLOT, J
影响因子：
5.4
作者：
Aasa-Chapman, MMI;Holuigue, S;Mcknight, A
通讯作者：
Mcknight, A
影响因子：
5.4
作者：
Binley, JM;Klasse, PJ;Moore, JP
通讯作者：
Moore, JP