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Dopamine receptor activation increases HIV entry into primary human macrophages
Peter J Gaskill1, Hideaki H Yano2, Ganjam V Kalpana3
1Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
Plos One
|October 1, 2014
Summary
Dopamine increases HIV entry into macrophages, a key step in brain infection and neurocognitive disorders. This effect is dopamine receptor-dependent and suggests drug abuse may worsen HIV progression in the central nervous system.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Macrophages are the primary cells infected by HIV in the central nervous system (CNS).
- HIV infection of CNS macrophages contributes to neuropathogenesis and HIV-associated neurocognitive disorders (HAND).
- Drug abusers exhibit elevated CNS dopamine, a neurotransmitter linked to addiction.
Purpose of the Study:
- To investigate the impact of dopamine on HIV entry into primary human macrophages.
- To elucidate the mechanisms underlying dopamine's effect on HIV infection.
Main Methods:
- Primary human macrophages were exposed to dopamine during HIV infection.
- HIV entry was quantified using R5-tropic HIV.
- CCR5 dependency was assessed using the inhibitor TAK779.
- Dopamine receptor activation was evaluated using the antagonist flupenthixol.
Main Results:
- Dopamine exposure significantly increased R5-tropic HIV entry into macrophages.
- This increase was CCR5-dependent and occurred above a dopamine concentration of 10^8 M.
- The effect required dopamine receptor activation and involved both dopamine receptor subtypes.
Conclusions:
- Dopamine enhances HIV entry into macrophages, potentially impacting HIV pathogenesis in the CNS.
- Elevated CNS dopamine levels in drug abusers may exacerbate neuroinflammation and contribute to HAND.
- This highlights a common mechanism by which diverse drugs of abuse can worsen HIV outcomes.
