Sustained type I interferon signaling after human immunodeficiency virus type 1 infection of human iPSC derived microglia and cerebral organoids

Sustained type I interferon signaling after human immunodeficiency virus type 1 infection of human iPSC derived microglia and cerebral organoids

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Summary: Human immunodeficiency virus type-1 (HIV-1)-associated neurocognitive disorder (HAND) affects up to half of people Bike Parts - Miscellaneous - Nuts living with HIV-1 and causes long term neurological consequences.The pathophysiology of HIV-1-induced glial and neuronal functional deficits in humans remains enigmatic.To bridge this gap, we established a model simulating HIV-1 infection in the central nervous system using human induced pluripotent stem cell (iPSC)-derived microglia combined with sliced neocortical organoids.Incubation of microglia with two replication-competent macrophage-tropic HIV-1 strains (JRFL and YU2) elicited productive infection and inflammatory activation.RNA sequencing revealed significant and sustained activation of type I interferon signaling pathways.

Incorporating Brushes microglia into sliced neocortical organoids extended the effects of aberrant type I interferon signaling in a human neural context.Collectively, our results illuminate a role for persistent type I interferon signaling in HIV-1-infected microglia in a human neural model, suggesting its potential significance in the pathogenesis of HAND.