Broad-Spectrum Antiviral Activity of an Ankyrin Repeat Protein on Viral Assembly against Chimeric NL4-3 Viruses Carrying Gag/PR Derived from Circulating Strains among Northern Thai Patients

Sakkhachornphop, Supachai and Hadpech, Sudarat and Wisitponchai, Tanchanok and Panto, Chansunee and Kantamala, Doungnapa and Utaipat, Utaiwan and Praparattanapan, Jutarat and Kotarathitithum, Wilai and Taejaroenkul, Sineenart and Yasamut, Umpa and Chupradit, Koollawat and Moonmuang, Sutpirat and Lee, Vannajan Sanghiran and Suparatpinyo, Khuanchai and Tayapiwatana, Chatchai (2018) Broad-Spectrum Antiviral Activity of an Ankyrin Repeat Protein on Viral Assembly against Chimeric NL4-3 Viruses Carrying Gag/PR Derived from Circulating Strains among Northern Thai Patients. Viruses, 10 (11). p. 625. ISSN 1999-4915, DOI https://doi.org/10.3390/v10110625.

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Official URL: https://doi.org/10.3390/v10110625

Abstract

Certain proteins have demonstrated proficient human immunodeficiency virus (HIV-1) life cycle disturbance. Recently, the ankyrin repeat protein targeting the HIV-1 capsid, AnkGAG1D4, showed a negative effect on the viral assembly of the HIV-1NL4-3 laboratory strain. To extend its potential for future clinical application, the activity of AnkGAG1D4 in the inhibition of other HIV-1 circulating strains was evaluated. Chimeric NL4-3 viruses carrying patient-derived Gag/PR-coding regions were generated from 131 antiretroviral drug-naïve HIV-1 infected individuals in northern Thailand during 2001⁻2012. SupT1, a stable T-cell line expressing AnkGAG1D4 and ankyrin non-binding control (AnkA32D3), were challenged with these chimeric viruses. The p24CA sequences were analysed and classified using the K-means clustering method. Among all the classes of virus classified using the p24CA sequences, SupT1/AnkGAG1D4 demonstrated significantly lower levels of p24CA than SupT1/AnkA32D3, which was found to correlate with the syncytia formation. This result suggests that AnkGAG1D4 can significantly interfere with the chimeric viruses derived from patients with different sequences of the p24CA domain. It supports the possibility of ankyrin-based therapy as a broad alternative therapeutic molecule for HIV-1 gene therapy in the future.

Item Type: Article
Funders: Thailand Research Fund through the Royal Golden Jubilee program (Grant PHD/0146/2556 and PHD/0184/2557)
Uncontrolled Keywords: HIV-1; Gag polyprotein; virus assembly inhibitor; ankyrin; protein therapy
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Divisions: Faculty of Science > Department of Chemistry
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 05 Apr 2019 07:42
Last Modified: 05 Apr 2019 07:42
URI: http://eprints.um.edu.my/id/eprint/20807

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