Polypeptides inhibit HIV-1 replication by interfering viral Vpu-mediated tetherin degradation
Abstracts: 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 t...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-09-01
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| Series: | Infectious Medicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772431X23000394 |
| Summary: | Abstracts: 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. |
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| ISSN: | 2772-431X |