HIV潜伏感染激活剂的研究进展

Research Progress in HIV Latency-reversing Agents

艾滋病是由人类免疫缺陷病毒(Human immunodeficiency virus,HIV)引起的人类最严重的单一病因疾病,以全身免疫系统严重损害为特征。高效抗逆转录病毒疗法(Highly active anti-retroviral therapy,HAART)的应用已经成功地将艾滋病从一种致死性疾病转变为慢性可控性疾病。但长期接受HAART治疗的艾滋病患者一旦停药,患者体内潜伏的HIV会迅速反弹。艾滋病无法彻底治愈的原因是患者体内HIV病毒潜伏储存库的存在。"Shock and kill"策略是使用HIV潜伏感染激活剂(Latency-reversing agents,LRAs)诱导潜伏HIV前病毒复制及表达,然后联合HAART将病毒一网打尽,同时由于细胞病变效应和/或HIV特征性免疫反应使潜伏细胞的半衰期大大缩短,最终达到功能性治愈的目的。因此,高效、安全且特异性促进潜伏库衰减的LRAs成为现今艾滋病治愈研究的热点。本文聚焦国内外前沿研究,对具有临床发展前景的HIV潜伏感染激活剂做一综述,为未来LRAs药物的研发指明方向。

Acquired immunodeficiency syndrome （AIDS） is one of the most serious diseases caused by infection with the human immunodeficiency virus （HIV）. In AIDS, severe loss of the cellular immunity of the body occurs. Currently, the classification of AIDS has changed from a ＂fatal disease＂ to a ＂manageable chronic disease＂ by highly active antiretroviral therapy （HAART）. HAART is long-term treatment of AIDS but, once it is withdrawn, the latent HIV in the body rebounds rapidly. Complete eradication of HIV with HAART does not seem to be possible because a stable reservoir of HIV latent infection is present in HIV-infected patients. One of the most challenging issues in HIV-1 latent infection is how to kill the integrated previruses on the host target cells and diminish the HIV reservoir. A ＂shock and kill＂ strategy is to use latency-reversing agents （LRAs） to induce replication and expression of latent HIV, and then combinatorial HAART to kill the virus. Otherwise, because of cytopathic effects and/or characteristic HIV immune responses, the half-life of HIV latent cells will be reduced greatly. Therefore, LRAs with high efficiency, safety and specificity to promote the attenuation of latent libraries have become important in the research of a functional cure for HIV. This review introduces the latest research progress in LRA development.