以Tat为靶点的人类免疫缺陷病毒1型潜伏库治疗策略的研究进展

打开文本图片集

[中图分类号] R512.91 [文献标志码] A

ABSTRACTHuman immunodeficiency virus type 1（HIV-1） latent reservoirs pose the primary obstacle to curing acquired immunodeficiency syndrome （AIDS）. Transactivator（Tat），a regulatory protein encoded by HIV-1，influences the establishment and reactivation of latent reservoirs by promoting viral transcription. Inhibitors targeting Tat protein suppress viral rebound by reducing Tat protein levels and disrupting its transcription-promoting functions. Among the two strategies for treating HIV-1 latent reservoirs，the“block-and-lock”strategy，which is based on Tat protein inhibitors，aims to target HIV-1 proteins or host factors while interfering with histone epigenetic modifications，thereby permanently silencing proviral DNA and maintaining HIV-1 latency even after treatment discontinuation. Tat-related inhibitors such as didehydrocortistatin A（dCA），triptolide，and apalutamide-derived Q3O8 regulate HIV-1 latency through distinct mechanisms. This review summarizes the regulatory roles of Tat in HIV-l latency， Tat protein inhibitor-based therapeutic strategies for targeting latent reservoirs，and the mechanisms of action of related inhibitors，with the goal of providing insights for the development of drugs toward achieving functional HIV-1 cure.

KEYWORDSAcquired immunodeficiency syndrome； Transactivator；HIV-1 latent reservoir；“Blockand-lock” strategy；Functional cure

人类免疫缺陷病毒（human immunodeficiencyvirus，HIV）起源于非洲黑猩猩非人灵长类动物猿类免疫缺陷病毒，于1983年被首次发现并成功分离[]。（剩余17553字）