Immunity:新方法清除潜伏HIV
艾滋病毒会在免疫系统的T细胞内长期处于休眠、失活状态,即使通过服用药物能有效地停止其繁殖,以感染其他细胞。但是,一旦治疗停止或中断后,潜伏状态的病毒又会迅速重新激活,以往研究人员说这几乎证明消灭这些隐藏的感染病毒(pockets of infection)是不可能。所以最有希望能最终治愈疾病的方式就是强制使得潜伏的病毒暴露,使所谓的免疫系统的细胞毒性“杀手”T细胞能“看得见”它们,然后用药品辅助以消除体内感染的细胞。最近约翰霍普金斯大学Siliciano教授实验室介绍了一种免疫接种策略来实现这个愿望,相关成果在线发表在3月8日《Immunity》上。
在他们的研究报告中,Siliciano表明在潜伏的病毒被激活后,受感染的CD4T细胞会存活。当其他免疫系统的CD8T细胞能被其激活时,上述受感染的CD4T细胞才会被杀死。Siliciano和他的同事们详细描述了他们的疫苗接种策略以及如何只在潜伏期病毒激活前,就引入一种分子量小的艾滋病毒蛋白以激活能对抗艾滋病病毒的T细胞反应。这种不完整的病毒蛋白以及随后的免疫系统疫苗接种能生产足够的细胞毒性T细胞攻击并杀死潜伏的感染细胞。
Siliciano和他的研究团队下一个计划就是在潜伏的病毒激活前,测试促进免疫反应的不同方法,并比较其清除所有受艾滋病毒感染细胞的有效性。
转自http://www.bioon.com/biology/Immunology/519277.shtml 有改动
Stimulation of HIV-1-Specific Cytolytic T Lymphocytes Facilitates Elimination of Latent Viral Reservoir after Virus Reactivation
Liang Shan, Kai Deng, Neeta S. Shroff, Christine M. Durand, S. Alireza. Rabi, Hung-Chih Yang, Hao Zhang, Joseph B. Margolick, Joel N. Blankson, Robert F. Siliciano
Highly active antiretroviral therapy (HAART) suppresses HIV-1 replication but cannot eliminate the virus because HIV-1 establishes latent infection. Interruption of HAART leads to a rapid rebound of viremia, so life-long treatment is required. Efforts to purge the latent reservoir have focused on reactivating latent proviruses without inducing global T cell activation. However, the killing of the infected cells after virus reactivation, which is essential for elimination of the reservoir, has not been assessed. Here we show that after reversal of latency in an in vitro model, infected resting CD4+ T cells survived despite viral cytopathic effects, even in the presence of autologous cytolytic T lymphocytes (CTLs) from most patients on HAART. Antigen-specific stimulation of patient CTLs led to efficient killing of infected cells. These results demonstrate that stimulating HIV-1-specific CTLs prior to reactivating latent HIV-1 may be essential for successful eradication efforts and should be considered in future clinical trials
原文链接 http://www.cell.com/immunity/abstract/S1074-7613(12)00084-2
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