Ingenol Protects Human T Cells From HIV-1 Infection

OBJECTIVES: Many natural compounds have been investigated as drug candidates to prevent human immunodeficiency virus (HIV) with low cytotoxicity. We tested whether ingenol from Euphorbia ingens exerts anti-HIV effects in human T cell lines. METHODS AND RESULTS: Ingenol effectively maintained high cell viability (CD(50), >1 mM) in H9 and MT4 T cells. The efficacy of ingenol to inhibit HIV-1 infection was dose dependent. ED(50) for 100 and 200 TCID(50) of HIV-1 was 5.06 and 16.87 μM, respectively. Gag p24 antigen production in ingenol-treated MT4 cells was reduced by 24.5% on day 6 post-infection. While p24 antigen was reduced in ingenol-treated cells, levels of cytokines such as TNF-α and IL-6 and chemokines such as RANTES and MCP-1 were increased. dUTP level related to late apoptotic events was increased on day 2 post-infection of HIV by ingenol treatment, whereas expression of annexin V was unchanged. Reduced levels of iNOS and ZAP-70 after HIV infection were recovered by ingenol treatment. CONCLUSION: Ingenol helps T cells to survive longer against viremia after HIV-1 infection, without exerting cytotoxic effects. Ingenol can be considered a safe and efficacious candidate for immune-boosting therapy for AIDS patients.