Curcuma Longa Induces the Transcription Factor FOXP3 to Downregulate Human Chemokine CCR5 Expression and Inhibit...

Area of Science:

• Virology and Immunology
• Natural Product Chemistry
• Molecular Biology

Background:

• Combination antiretroviral therapy (cART) for HIV has limitations including drug resistance and adverse effects.
• Novel antivirals are needed, and natural products like curcumin show promise.
• Curcumin, from turmeric, possesses known anti-inflammatory and antioxidant properties.

Purpose of the Study:

• To evaluate curcumin's inhibitory effects on HIV-1 in vitro.
• To elucidate the mechanism of action, focusing on CCR5 and FOXP3.
• To explore curcumin's potential as a safe antiviral agent.

Main Methods:

• HIV-1 pseudovirus infectivity assays using HEK293T cells.
• Molecular docking analysis of curcumin with CCR5 and HIV-1 RNase H/RT.
• Cell cytotoxicity, transcriptome sequencing, and assessment of CCR5/FOXP3 levels.
• Transfection assays, luciferase reporter assays, and chromatin immunoprecipitation (ChIP).

Main Results:

• Curcumin demonstrated dose-dependent inhibition of HIV-1 infection, comparable to zidovudine (AZT).
• Molecular docking showed significant binding affinity of curcumin to CCR5 and HIV-1 RNase H/RT.
• Curcumin inactivated the transcription factor FOXP3, decreasing CCR5 expression and inhibiting PI3K-AKT activation.
• Curcumin inhibited FOXP3-mediated CCR5 promoter transactivation and HIV-1 virion production.

Conclusions:

• Curcumin exhibits significant in vitro anti-HIV-1 activity.
• The mechanism involves inactivation of FOXP3, leading to reduced CCR5 expression.
• Curcumin warrants further investigation as a potential dietary agent to reduce CCR5-tropic HIV-1 virulence.