Persistent neuroinflammation in HIV-1 infected brain organoid models treated with antiretroviral therapy 3151

Résumé fourni par la source

Abstract Description HIV-1-associated neurocognitive impairment (HIV-1-NCI) is characterized by chronic neuroinflammation and a decline in neuronal function, even when antiretroviral therapy (ART) successfully suppresses viral replication. Microglia, the primary reservoir of HIV-1 within the central nervous system (CNS), plays a critical role in maintaining this neuroinflammatory state. However, understanding how chronic neuroinflammation is generated and sustained by HIV-1, or impacted by ART, is still unknown. We established an in vitro model of microglia derived from admixed hematopoietic progenitor cells (HPC) embedded into embryonic stem cell (ESC)-derived Brain Organoids (BO). HIV-1 infected microglia were co-cultured and infiltrated into BOs. We assessed inflammation through cytokine and phospho-NF-kB levels using flow cytometry and confocal microscopy. Although microglia were the primary source of pro-inflammatory cytokines, astrocytes, neurons and neural stem cells also exhibited increased phospho-NF-kB levels, indicating a broader neuroinflammatory response. ART effectively suppressed the virus to levels below detection but did not decrease neuroinflammation. Although ART significantly suppressed HIV-1, neuronal inflammation persisted in ART-treated, HIV-1 infected BOs. Together, these findings demonstrate that HIV-1 infection of microglia infiltrated into BOs provides a robust in vitro model for understanding the impact of HIV-1 and ART on neuroinflammation. Funding Sources Funding: NIH RO1 DA052527 Topic Categories Neuroimmunology (NEUR)

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.