UM15 reinforces a lymphocyte-mimicking nanotrap for precise HIV-1 inhibition  

作　　者：Jinbang Zhang Zhengyang Li Jiaxin Li Hui Li Junwei Che Te Zhao Pengfei Zou Jingwan Han Yang Yang Meiyan Yang Yuli Wang Wei Gong Haihua Xiao Zhiping Li Lin Li Chunsheng Gao 

机构地区：[1]State key Laboratory of Toxicology and Medical Countermeasure,Beijing Institute of Pharmacology and Toxicology,Beijing 100039,China [2]Pharmaceutical College,Henan University,Kaifeng 475001,China [3]State Key Laboratory of Pathogen and Biosecurity,Beijing Institute of Microbiology and Epidemiology,Beijing 100071,China [4]School of Public Health and Health Management,Gannan Medical University,Ganzhou 341000,China [5]Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190,China

出　　处：《Nano Research》2023年第7期9906-9920,共15页纳米研究（英文版）

基　　金：The current work was supported by the National Natural Science Foundation of China(No.81502675).

摘　　要：Even the potential of T cell-mimicking nanotrap for long term viral control due to its overcoming of human immunodeficiency virus(HIV)genetic diversity and viral resistance,the robust HIV inhibition was not expected because these nanotraps displayed no obvious advantages compared with the infinite host cells.Herein,a glycoprotein 120(gp120)-targeting polypeptide UM15 reinforced lymphocyte-mimicking nanotrap was constructed,and its improved HIV-1 inhibiting efficacy was validated.According to the results,the constructed nanotraps exhibited evident escaping ability from uptake of the mononuclear phagocyte system and highly improved binding ability with gp120 proteins.The constructed nanotraps neutralized all tested HIV-1 pseudo typed viruses with IC80 of 21.0μg/mL,and inhibited both X4-tropic and R5-tropic HIV-1 with IC80 of 34.4 and 20.6μg/mL,respectively.Approximately 40%of gp120 was observed to be shed from pseudo virus,and above 40%bystander T cells were prevented from gp120-induced death by the constructed nanotraps.The safety of the constructed nanotraps was confirmed both in vitro and in mice.Therefore,the constructed nanotraps could specifically neutralize free HIV-1,selectively bind with gp120 expressing HIV-1 infected cells,cause gp120 shedding,inhibit gp120-induced bystander T cell killing on the premise of safety,and were considered as promising therapeutic agents for precise inhibition of HIV.

关 键 词：nanotrap lymphocyte membrane UM15 human immunodeficiency virus-1(HIV-1) glycoprotein 120(gp120) 

分 类 号：R51[医药卫生—内科学]