HIV Latency-Reversing Agents Have Diverse Effects on Natural Killer Cell Function

Area of Science:

• Immunology
• Virology
• Pharmacology

Background:

• Achieving durable therapy-free remission for HIV infection requires clearing latent virus.
• Latency-reversing agents (LRAs) are being developed to reactivate latent HIV for immune clearance.
• Understanding LRA effects on immune effector cells, like natural killer (NK) cells, is crucial.

Purpose of the Study:

• To assess the impact of specific LRAs on primary NK cell function.
• To evaluate how histone deacetylase inhibitors and protein kinase C agonists affect NK cell antiviral activity, cytotoxicity, cytokine secretion, phenotype, and viability.

Main Methods:

• Primary NK cells were exposed ex vivo to three histone deacetylase inhibitors (SAHA/vorinostat, romidepsin, panobinostat) and two protein kinase C agonists (prostratin, ingenol).
• NK cell antiviral activity, cytotoxicity, cytokine secretion, phenotype, and viability were assessed.

Main Results:

• Vorinostat showed minimal impact on NK cell parameters.
• Panobinostat decreased NK cell viability, antiviral activity, and cytotoxicity.
• Prostratin induced non-specific NK cell activation and enhanced antiviral activity.

Conclusions:

• LRAs can significantly alter NK cell function and viability.
• These modulatory effects on NK cells must be carefully considered in developing HIV remission strategies.
• Further research is needed to optimize LRA use for effective HIV clearance.