Conclusions
RNA profiling of bdEVs and source tissues reveals potential regulatory networks in SIV infection and SIV-related CNS pathology.
Methods
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 sequencing and qPCR to detect mRNA, miRNA, and circRNA levels.
Results
Multiple dysregulated bdEV RNAs, including mRNAs, miRNAs, and circRNAs, were identified in acute infection and chronic infection with pathology. Most dysregulated mRNAs in bdEVs reflected dysregulation in their source tissues. These mRNAs are disproportionately involved in inflammation and immune responses, especially interferon pathways. For miRNAs, qPCR assays confirmed differential abundance of miR-19a-3p, let-7a-5p, and miR-29a-3p (acute SIV infection), and miR-146a-5p and miR-449a-5p (chronic with pathology) in bdEVs. In addition, target prediction suggested that several circRNAs that were differentially abundant in source tissue might be responsible for specific differences in small RNA levels in bdEVs during SIV infection. Conclusions: RNA profiling of bdEVs and source tissues reveals potential regulatory networks in SIV infection and SIV-related CNS pathology.