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Updated: Jul 8, 2025
Peptide-based Identification of Functional Motifs and their Binding Partners
Published on: June 30, 2013
Polypeptides inhibit HIV-1 replication by interfering viral Vpu-mediated tetherin degradation
Shuai Chang1, Lifeng Cai2, Yongchang Yang1
1Department of Clinical Laboratory, Seventh Medical Center of Chinese PLA General Hospital, No. 5 Nanmencang, Dongcheng District, Beijing 100700, China.
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 sequence 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 tetherin at atomic resolution and the development of small molecules inhibitors targeting Vpu-tetherin interactions may open a new avenue for novel antiretroviral therapy.
