Neuroinflammation and EIF2 Signaling Persist despite Antiretroviral Treatment in an hiPSC Tri-culture Model of HIV Infection

• DOI: 10.1016/j.stemcr.2020.02.010
• Publication Date: 2020-03-26T14:36:31Z
• Authors: Sean K. Ryan; Michael V. Gonzalez; James P. Garifallou; Frederick C. Bennett; Kimberly S. Williams; Nathaniel P. Sotuyo; Eugene Mironets; Kieona Cook; Hakon Hakonarson; Stewart A. Anderson; Kelly L. Jordan-S...
• Keywords: Efavirenz

HIV-associated neurocognitive disorders (HAND) affect over half of HIV-infected individuals, despite antiretroviral therapy (ART). Therapeutically targetable mechanisms underlying HAND remain elusive, partly due to a lack representative model. We developed human-induced pluripotent stem cell (hiPSC)-based model, independently differentiating hiPSCs into neurons, astrocytes, and microglia, systematically combining generate tri-culture with or without HIV infection ART. Single-cell RNA sequencing analysis on tri-cultures microglia revealed inflammatory signatures in the EIF2 signaling all three types. Treatment compound efavirenz (EFZ) mostly resolved these signatures. However, EFZ increased RhoGDI CD40 microglia. This activation was associated persistent increase transforming growth factor α production by work establishes that recapitulates key features CNS provides new model examine effects infection, its treatment, other co-morbid conditions.