Polypeptides inhibit HIV-1 replication by interfering viral Vpu-mediated tetherin degradation  

作　　者：Shuai Chang Lifeng Cai Yongchang Yang Binlian Sun Jingyun Li Jie Liu Lin Li 

机构地区：[1]Department of Clinical Laboratory,Seventh Medical Center of Chinese PLA General Hospital,No.5 Nanmencang,Dongcheng District,Beijing 100700,China [2]Department of AIDS Research,State Key Laboratory of Pathogen and Biosecurity,Beijing Institute of Microbiology and Epidemiology,20 Dongda Street,Beijing 100071,China [3]Wuhan Institute of Biomedical Sciences,School of Medicine,Jianghan University,Wuhan 430056,China

出　　处：《Infectious Medicine》2023年第3期224-228,共5页感染医学（英文）

摘　　要：Background:HIV-1 Vpu acts by counteracting the tethering function of tetherin and resulting in the release of HIV-1 virion.Disrupting Vpu-tetherin interactions may provide a promising new target for antiretroviral therapy.Methods:Polypeptides that covered the amino acid sequence on the interface of Vpu-tetherin complex were designed.Phenotypic susceptibilities and cellular toxicities to the polypeptides were measured.The mechanisms of the anti-HIV-1 polypeptides were determined by the Western blot analysis and laser confocal scanning.Seven 20-mer polypeptides from wild-type Vpu amino acid sequence were designed.Results:We report the design and identification of 3 novel anti-HIV-1 polypeptides that derived from Vpu se-quence which can efficiently inhibit HIV-1 infection.A pilot mechanism study showed that the active polypeptide could counteract Vpu-mediated tetherin downregulation.Laser confocal image scanning study showed that the polypeptides bound on the cell surface with a receptor specific binding manner,which may target tetherin that expressed on cell surface.Conclusion:Our work provided first evidence that counteracting Vpu-mediated tetherin downregulation could be a target for novel anti-HIV-1 drug design.Future works to provide direct evidence of inhibitors interact with teth-erin at atomic resolution and the development of small molecules inhibitors targeting Vpu-tetherin interactions may open a new avenue for novel antiretroviral therapy.

关 键 词：ANTIRETROVIRAL HIV-1 POLYPEPTIDE VPU TETHERIN 

分 类 号：R512.91[医药卫生—内科学]