Translating the Brain Transcriptome in NeuroAIDS: From Non-human Primates to Humans

• Published in: Journal of neuroimmune pharmacology 2012-06, Vol.7 (2), p.372-379
• Main Authors: Winkler, Jessica M., Chaudhuri, Amrita Datta, Fox, Howard S.
• Format: Article
• Language: English
• Subjects: AIDS Dementia Complex - genetics; AIDS Dementia Complex - metabolism; Algorithms; Animal models; Animals; antiretroviral therapy; Biomedical and Life Sciences; Biomedicine; Brain; Brain - metabolism; Cell Biology; Coding; Computational neuroscience; Disease Models, Animal; Gene expression; Gene Expression Profiling; Genomes; Haplorhini; Human immunodeficiency virus; Humans; Immune response; Immunology; Inflammation; Invited Review; Ion channels; MicroRNAs - analysis; miRNA; Monkeys & apes; Neurosciences; non-coding RNA; Pharmacology/Toxicology; Primates; Reviews; Simian Acquired Immunodeficiency Syndrome - genetics; Simian Acquired Immunodeficiency Syndrome - metabolism; Simian immunodeficiency virus; Stat1 protein; Transcription; Transcriptome; Virology
• ISSN: 1557-1890; 1557-1904
• DOI: 10.1007/s11481-012-9344-5

In the post-human genome project era, high throughput techniques to detect and computational algorithms to analyze differentially expressed genes have proven to be powerful tools for studying pathogenesis of neuroAIDS. Concurrently, discovery of non-coding RNAs and their role in development and disease has underscored the importance of examining the entire transcriptome instead of protein coding genes alone. Herein, we review the documented changes in brain RNA expression profiles in the non-human primate model of neuroAIDS (SIV infected monkeys) and compare the findings to those resulting from studies in post-mortem human samples of neuroAIDS. Differential expression of mRNAs involved in inflammation and immune response are a common finding in both monkey and human samples – even in HIV infected people on combination antiretroviral therapy, a shared set of genes is upregulated in the brains of both infected monkeys and humans: B2M, IFI44, IFIT3, MX1, STAT1. Additionally, alterations in ion channel encoding genes have been observed in the human studies. Brain miRNA profiling has also been performed, and up-regulation of two miRNAs originating from the same transcript, miR-142-3p and miR-142-5p, is common to human and monkey neuroAIDS studies. With increases in knowledge about the genome and advances in technology, unraveling alterations in the transcriptome in the SIV/monkey model will continue to enrich our knowledge about the effects of HIV on the brain.