The HIV-1 gag p6: a promising target for therapeutic intervention

• Published in: Retrovirology Vol. 21; no. 1; pp. 1 - 7
• Main Authors: Chen, Xiaowei, Wang, Xiao
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 23-01-2024; BioMed Central; BMC
• Subjects: ALG-2-interacting protein; Anti-Retroviral Agents; Antiretroviral agents; Antiretrovirals; Antiviral agents; Binding sites; Biological Transport; Cell cycle; Cell Membrane; Development and progression; Disease susceptibility; Drug development; Endosomal Sorting Complexes Required for Transport; Gag protein; Health aspects; Highly active antiretroviral therapy; HIV; HIV (Viruses); HIV-1; HIV-1 Gag p6; Human immunodeficiency virus; Humans; Kinases; Life cycles; Mediation; Mutation; NMR; Nuclear magnetic resonance; Phosphorylation; Protein X; Proteins; Replication; Review; Signal transduction; SUMO protein; Ubiquitin; Ubiquitination; Viral infections; Viral replication and budding; Virions; Viruses; Vpr protein; HIV-1 Gag p6; Antiretrovirals; Viral replication and budding
• ISSN: 1742-4690; 1742-4690
• DOI: 10.1186/s12977-024-00633-2

The p6 domain of the Gag precursors (Gag p6) in human immunodeficiency virus type 1 (HIV-1) plays multifunctional roles in the viral life cycle. It utilizes the endosomal sorting complex required for transport (ESCRT) system to facilitate viral budding and release from the plasma membrane through the interactions with the ESCRT-I component tumor susceptibility gene 101 (TSG101) and with the ALG-2 interacting protein X (ALIX). Moreover, Gag p6 contributes to viral replication by a range of posttranslational modifications such as SUMOylation, ubiquitination and phosphorylation. Additionally, Gag p6 also mediates the incorporation of the accessory protein Vpr into virions, thereby promoting Vpr-induced viral replication. However, less attention is focused on Gag p6 as therapeutic intervention. This review focuses on the structures and diverse functions of Gag p6 in viral replication, host cells, and pathogenesis. Additionally, several challenges were also discussed in studying the structure of Gag p6 and its interactions with partners. Consequently, it concludes that the Gag p6 represents an attractive target for the development of antiretroviral drugs, and efforts to develop p6-targeted antiretrovirals are expected to undergo significant growth in the forthcoming years.