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Morphine potentiates HIV infection and receptor expression in 3d brain organoids

Michael Swingler1, Doga Tasdemir1, Senem Cakir1

  • 1Department of Microbiology, Immunology, and Inflammation, Center for Neurovirology and Gene Editing, Temple University Lewis Katz School of Medicine, Philadelphia, PA, USA.

Journal of Neurovirology
|May 18, 2026
PubMed

Insights

Morphine directly increases HIV receptors in the brain, boosting viral load. This study reveals a brain-specific mechanism for how opioids worsen HIV infection, independent of the body.

Area of Science:

  • Neuroscience
  • Virology
  • Immunology

Background:

  • Opioid abuse is a significant comorbidity in HIV patients.
  • The direct impact of opioids on HIV within the central nervous system (CNS) is not fully understood.

Purpose of the Study:

  • To investigate the direct effects of morphine on HIV replication in the brain.
  • To elucidate brain-intrinsic mechanisms of opioid-mediated viral enhancement in neuroHIV.

Main Methods:

  • Utilized induced pluripotent stem cell-derived 3D human cerebral organoids (hCOs).
  • Assessed the expression of HIV receptors (CD4, CCR5, CXCR4) following morphine exposure.
  • Quantified HIV viral load within the hCOs.

Main Results:

  • Morphine directly upregulated HIV receptors CD4, CCR5, and CXCR4 in hCOs.
  • This upregulation significantly increased HIV viral load within the CNS.
  • Demonstrated opioid-mediated viral enhancement independent of peripheral immune cells or a blood-brain barrier.

Conclusions:

  • Human cerebral organoids serve as a valuable platform for studying neuroHIV.
  • Opioids can directly amplify CNS HIV infection through brain-intrinsic mechanisms.
  • Findings highlight a novel pathway for opioid-induced exacerbation of HIV in the brain.
Keywords:
Cerebral organoidsHIV-1InfectionMorphineOpioidsVirus

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