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

J Neurovirol. 2026 May 18;32(3):19. doi: 10.1007/s13365-026-01316-8.

Abstract

Opioid abuse is a major comorbidity of HIV, yet its direct effects on the brain remain unclear. Using iPSC-derived 3D human cerebral organoids (hCOs), we show that morphine directly upregulates HIV receptors CD4, CCR5, and CXCR4 in the absence of peripheral immune cells or a blood-brain barrier. This receptor induction drives a significant increase in HIV viral load within the CNS, revealing a brain-intrinsic mechanisms of opioid-mediated viral enhancement. These findings establish hCOs as a unique platform to investigate neuroHIV and provide critical insight into how opioids amplify CNS infection independently of peripheral factors.

Keywords: Cerebral organoids; HIV-1; Infection; Morphine; Opioids; Virus.

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Brain* / drug effects
  • Brain* / metabolism
  • Brain* / virology
  • CD4 Antigens / genetics
  • CD4 Antigens / metabolism
  • HIV Infections* / genetics
  • HIV Infections* / metabolism
  • HIV Infections* / pathology
  • HIV Infections* / virology
  • HIV-1* / drug effects
  • Humans
  • Induced Pluripotent Stem Cells / drug effects
  • Induced Pluripotent Stem Cells / metabolism
  • Induced Pluripotent Stem Cells / virology
  • Morphine* / pharmacology
  • Organoids* / drug effects
  • Organoids* / metabolism
  • Organoids* / virology
  • Receptors, CCR5* / genetics
  • Receptors, CCR5* / metabolism
  • Receptors, CXCR4* / genetics
  • Receptors, CXCR4* / metabolism
  • Viral Load / drug effects

Substances

  • Morphine
  • Receptors, CXCR4
  • CXCR4 protein, human
  • Receptors, CCR5
  • CD4 Antigens
  • CCR5 protein, human
  • Analgesics, Opioid