Melkova Zora, Shankaran Prakash, Madlenakova Michaela, Bodor Josef
Department of Immunology and Microbiology, 1st Faculty of Medicine, Charles University, Studnickova 7, 128 00, Prague 2, Czech Republic.
BIOCEV, Biotechnology and Biomedicine Center of the Academy of Sciences and Charles University in Vestec, Průmyslová 595, 252 50, Vestec, Czech Republic.
Folia Microbiol (Praha). 2017 Jan;62(1):73-87. doi: 10.1007/s12223-016-0474-7. Epub 2016 Oct 5.
HIV-1 infection cannot be cured as it persists in latently infected cells that are targeted neither by the immune system nor by available therapeutic approaches. Consequently, a lifelong therapy suppressing only the actively replicating virus is necessary. The latent reservoir has been defined and characterized in various experimental models and in human patients, allowing research and development of approaches targeting individual steps critical for HIV-1 latency establishment, maintenance, and reactivation. However, additional mechanisms and processes driving the remaining low-level HIV-1 replication in the presence of the suppressive therapy still remain to be identified and targeted. Current approaches toward HIV-1 cure involve namely attempts to reactivate and purge HIV latently infected cells (so-called "shock and kill" strategy), as well as approaches involving gene therapy and/or gene editing and stem cell transplantation aiming at generation of cells resistant to HIV-1. This review summarizes current views and concepts underlying different approaches aiming at functional or sterilizing cure of HIV-1 infection.
由于HIV-1感染持续存在于既不受免疫系统攻击也不受现有治疗方法作用的潜伏感染细胞中,所以无法治愈。因此,必须进行终身治疗,仅抑制活跃复制的病毒。潜伏库已在各种实验模型和人类患者中得到定义和表征,这有助于研究和开发针对HIV-1潜伏建立、维持和重新激活关键的各个步骤的方法。然而,在抑制性治疗存在的情况下,驱动剩余低水平HIV-1复制的其他机制和过程仍有待确定和靶向。目前针对HIV-1治愈的方法主要包括试图重新激活并清除潜伏感染的HIV细胞(即所谓的“激活并杀灭”策略),以及涉及基因治疗和/或基因编辑以及干细胞移植的方法,旨在生成对HIV-1具有抗性的细胞。本综述总结了旨在实现HIV-1感染功能性治愈或无菌性治愈的不同方法背后的当前观点和概念。