Curcumin inhibits HIV-1 by modulating FOXP3 and suppressing CCR5 via PI3K/AKT and JAK/STAT pathways

Area of Science:

• Immunology
• Virology
• Pharmacology

Background:

• HIV-1 persistence and immune dysregulation are major challenges despite antiretroviral therapy.
• Curcumin is a natural compound with low toxicity and potential therapeutic applications.

Purpose of the Study:

• To investigate the mechanism by which curcumin inhibits HIV-1.
• To explore the potential of curcumin as an adjuvant therapy for HIV-1.

Main Methods:

• Network pharmacology and molecular docking to identify key targets.
• Chromatin immunoprecipitation (CHIP) and electrophoretic mobility shift assay (EMSA) to study protein-DNA interactions.
• High-throughput sequencing, mass spectrometry, and co-immunoprecipitation (CO-IP) to analyze pathway crosstalk.

Main Results:

• Curcumin inhibits HIV-1 by simultaneously targeting the PI3K/AKT and JAK/STAT pathways.
• Curcumin downregulates the viral co-receptor CCR5 and the immune checkpoint factor FOXP3.
• Curcumin disrupts FOXP3 binding to the CCR5 promoter, reducing viral entry.
• STAT3 and AKT1 were identified as key molecular targets of curcumin.
• Crosstalk between PI3K/AKT and JAK/STAT pathways represents a viable therapeutic axis for HIV-1.

Conclusions:

• Curcumin's dual inhibition of PI3K/AKT and JAK/STAT pathways offers a novel mechanism for HIV-1 suppression.
• Curcumin's ability to downregulate CCR5 and disrupt FOXP3 binding provides a rationale for its use in reducing viral entry.
• The findings support the repurposing of curcumin as an adjunct to Highly Active Antiretroviral Therapy (HAART) for targeting HIV-1 reservoirs.