Innate immune responses reverse HIV cognitive disease in mice: Profile by RNAseq in the brain

Abstract

Antiretroviral therapy controls immunodeficiency in people with HIV but many develop mild neurocognitive disorder. Here we investigated HIV brain disease by infecting mice with the chimeric HIV, EcoHIV, and probing changes in brain gene expression during infection and reversal with polyinosinic-polycytidylic acid (poly I:C). EcoHIV-infected C57BL/6 mice were treated with poly I:C and monitored by assay of learning in radial arm water maze, RNAseq of striatum, and QPCR of virus burden and brain transcripts. Poly I:C reversed EcoHIV-associated cognitive impairment and reduced virus burden. Major pathways downregulated by infection involved neuronal function, these transcriptional changes were normalized by poly I:C treatment. Innate immune responses were the major pathways induced in EcoHIV-infected, poly I:C treated mice. Our findings provide a framework to identify brain cell genes dysregulated by HIV infection and identify a set of innate immune response genes that can block systemic infection and its associated dysfunction in the brain.