Defective iron homeostasis in human immunodeficiency virus type-1 latency

Area of Science:

• Immunology
• Virology
• Cell Biology

Background:

• Highly active antiretroviral therapy (HAART) controls HIV-1 but cannot eliminate latent reservoirs.
• Heme oxygenase-1 (HO-1) induction by hemin protects cells from HIV-1 infection.
• Targeting latent HIV-1 reservoirs is crucial for complete viral eradication.

Purpose of the Study:

• To investigate the effect of hemin on latently HIV-1-infected cells.
• To explore the mechanism of hemin-induced cytotoxicity in the context of HIV-1 latency.
• To evaluate hemin as a potential agent for targeting latent HIV-1 reservoirs.

Main Methods:

• Treatment of latently HIV-1-infected ACH-2 cells with hemin.
• Stimulation of ACH-2 cells with TNF-α or co-culture with monocyte-derived macrophages (MDMs).
• Assessment of virus production, cellular toxicity, and iron homeostasis markers (ferritin, ferroportin, HO-1).

Main Results:

• Hemin treatment stimulated HIV-1 production in ACH-2 cells.
• Subsequent TNF-α stimulation or MDM co-culture led to cytotoxicity and cell death.
• Cytotoxicity correlated with reduced ferritin and ferroportin, and absent HO-1, causing iron accumulation.
• Defective iron homeostasis was observed in activated ACH-2 cells.

Conclusions:

• Hemin induces iron toxicity in latently HIV-1-infected cells, leading to cell death.
• This iron dysregulation selectively targets the latent HIV-1 reservoir.
• Hemin-induced iron toxicity presents a novel strategy for eradicating persistent HIV-1 reservoirs.