Interleukin 18 stimulates HIV type 1 in monocytic cells

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Interleukin-18 (IL-18) is a cytokine known to induce T helper type 1 responses.
• Human Immunodeficiency Virus type 1 (HIV-1) establishes chronic infection, particularly in monocytic cells.
• Understanding factors that regulate HIV-1 production is crucial for developing therapeutic strategies.

Purpose of the Study:

• To investigate the effect of IL-18 on HIV-1 production in chronically infected monocytic cells.
• To elucidate the molecular mechanisms underlying IL-18-mediated HIV-1 induction.

Main Methods:

• Utilized the chronically HIV-1 infected U1 monocytic cell line.
• Assessed HIV-1 production using quantitative assays.
• Measured levels of cytokines (TNF, IL-6, IL-8) and activation of signaling pathways (p38 MAPK, NF-kappaB).
• Employed specific inhibitors and neutralizing antibodies for mechanistic studies.

Main Results:

• IL-18 treatment increased HIV-1 production by 5- to 30-fold in U1 cells.
• Inhibition of TNF and IL-6 partially reduced IL-18-stimulated HIV-1 production.
• IL-18 induced IL-6 production, and exogenous IL-6 enhanced HIV-1 production.
• Specific inhibition of p38 mitogen-activated protein kinase (MAPK) significantly reduced IL-18-induced HIV-1 production.
• IL-18 exposure led to increased NF-kappaB binding activity in nuclear extracts.

Conclusions:

• IL-18 acts as an inducer of HIV-1 production in monocytes.
• Tumor necrosis factor (TNF) and IL-6 play intermediate roles in IL-18-mediated HIV-1 induction.
• Activation of the p38 MAPK pathway and subsequent NF-kappaB nuclear translocation are key events in this process.