Induction of innate immune responses reverses HIV cognitive disease in mice: profile by RNAseq in the brain

The extent of HIV immunodeficiency and related diseases has been greatly reduced by suppressive antiretroviral therapy but roughly 50% of infected people continue to develop mild neurocognitive disorder. We established an experimental approach to investigate HIV brain disease by infection of wildtype mice with the chimeric HIV, EcoHIV. The toll-like receptor 3 ligand, polyinosinic-polycytodylic acid (poly I:C), was used to induce innate immune responses prior to or during EcoHIV infection resulting in prevention of infection or reduced virus burden and reversed behavioral disease, respectively. Here we employed RNAseq to profile brain gene expression in EcoHIV infected mice at the time of cognitive impairment and its reversal in infected, poly I:C treated mice. We confirmed RNAseq findings by QPCR of a small set of transcripts. The major pathways down-regulated by infection involved neuronal function and this dysregulation was largely reversed by poly I:C treatment. Innate immune responses were the major functional pathways induced in infected, poly I:C treated mice that were absent in infected, untreated mice. Our findings provide a framework to identify essential brain cell genes dysregulated by HIV infection and identify a complementary set of immune response genes that block infection and its associated brain disease. Overall design: To investigate the effect of Poly I:C in mice infection with the chimeric EcoHIV virus. Four groups: uninfected and infected, treated or not with Poly I:C, 3 mice each group. Brain tissue from the striatum was subjected to RNA sequencing. --------------------------- The authors have not provided information to group each sample in the respective group.