GSE209606
Morphine Alters Systemic Responses to SIV Infection of Rhesus Monkeys and Changes Brain Macrophage and Microglia Gene Expression Favoring Neuropathogenesis
In this study, we investigated longitudinal changes in response to SIV infection of rhesus monkeys in the presence of morphine, compared to animals administered saline, before and after cART treatment. Using single-cell and single-nucleus RNA sequencing (scRNA-seq and snRNA-seq), we examined the effect of morphine on brain-resident macrophages and microglia in these SIV-infected, cART-suppressed animals to better understand the factors responsible for the morphine-induced increased CNS reservoir and the role of opioids in neuropathogenesis. Overall design: We probed systemic parameters as well as performed single-cell examination of the targets for infection in the brain, microglia and macrophages to investigate the interaction of morphine and SIV to identify novel host specific immune and neurological pathologies. Morphine treatment created an immunosuppressive environment, blunting initial responses to SIV infection which persisted during suppressive antiretroviral drug (ARV) therapy. ARV concentrations and penetration into the cerebrospinal fluid and brain were unchanged by morphine. However, in microglia and brain macrophages, their transcriptional signature was transformed to a neurodegenerative phenotype.