Small RNA profiles of brain tissue and brain tissue-derived extracellular vesicles in simian immunodeficiency virus (SIV) infection and SIV-related central nervous system pathology
Antiretroviral treatment regimens can effectively control HIV replication and some aspects of disease progression. However, molecular events in end-organ diseases such as central nervous system (CNS) disease are not yet fully understood, and routine eradication of latent reservoirs is not yet in reach. Brain tissue-derived extracellular vesicles (bdEVs) act locally in the source tissue and may indicate molecular mechanisms in HIV CNS pathology. Regulatory RNAs from EVs have emerged as important participants in HIV disease pathogenesis. Using brain tissue and bdEVs from the simian immunodeficiency virus (SIV) model of HIV disease, we profiled messenger RNAs (mRNAs) and microRNAs (miRNAs), seeking to identify possible networks of RNA interaction in SIV infection and neuroinflammation. Overall design: Postmortem occipital cortex tissue were collected from pigtailed macaques: uninfected controls and SIV-infected subjects (acute phase and chronic phase with or without CNS pathology). bdEVs were separated and characterized in accordance with international consensus standards. RNAs from bdEVs and source tissue were used for small RNA sequencing to detect mRNA and miRNA levels.