Design and Characterization of Inhibitors of Cell-Mediated Degradation of APOBEC3G That Decrease HIV-1 Infectivity
The cytoplasmic human Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3 or A3) cytidine deaminases G and F (A3G and A3F) can block the spread of human immunodeficiency virus (HIV). HIV counteracts this cell-intrinsic defense through a viral protein called viral infectivity f...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-04-01
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| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/17/4/514 |
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| Summary: | The cytoplasmic human Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3 or A3) cytidine deaminases G and F (A3G and A3F) can block the spread of human immunodeficiency virus (HIV). HIV counteracts this cell-intrinsic defense through a viral protein called viral infectivity factor (Vif). Vif causes proteasomal degradation of A3G and A3F proteins (A3G/F) in HIV-producing cells to ensure infectivity of virions subsequently released from these cells. Here, we optimized a lead compound reported previously to boost cellular levels of A3G. The modified analogs designed, synthesized, and evaluated here inhibit cell-mediated post-translational degradation of A3G/F, whether Vif is present or not. This increases A3G/F incorporation into Vif-positive virions to decrease viral infectivity. The compounds and processes described here can facilitate the development of new anti-HIV therapeutics whose host-targeted effect may not be evaded by resistance-conferring mutations in HIV Vif. |
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| ISSN: | 1999-4915 |