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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月18日

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  • Michael Swingler,
  • Doga Tasdemir,
  • Senem Cakir,
  • Anna Bellizzi,
  • Martina Donadoni,
  • Ilker K. Sariyer

摘要

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.