RNA Landscapes of Brain and Brain-Derived Extracellular Vesicles in Simian Immunodeficiency Virus Infection and Central Nervous System Pathology
Date
2023-12-11
Journal Title
Journal ISSN
Volume Title
Publisher
The Journal of Infectious Diseases
Abstract
Background
Brain tissue-derived extracellular vesicles (bdEVs) act locally in the central nervous system (CNS) and may indicate molecular mechanisms in human immunodeficiency virus (HIV) CNS pathology. Using brain homogenate (BH) and bdEVs from a simian immunodeficiency virus (SIV) model of HIV disease, we identified RNA networks in SIV infection and neuroinflammation.
Methods
Postmortem occipital cortex samples were obtained from uninfected controls and SIV-infected subjects (acute and chronic phases with or without CNS pathology [SIV encephalitis]). bdEVs were separated and characterized per international consensus guidelines. RNAs from bdEVs and BH were sequenced and quantitative polymerase chain reaction (qPCR)-amplified to detect levels of small RNAs (sRNAs, including microRNAs [miRNAs]) and longer RNAs including messenger RNAs (mRNAs) and circular RNAs (circRNAs).
Results
Dysregulated RNAs in BH and bdEVs were identified in acute and chronic infection with pathology groups, including mRNAs, miRNAs, and circRNAs. Most dysregulated mRNAs in bdEVs reflected dysregulation in source BH. These mRNAs are disproportionately involved in inflammation and immune responses. Based on target prediction, several circRNAs that were differentially abundant in source tissue might be responsible for specific differences in sRNA 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.
Description
This is a pre-copyedited, author-produced version of an article accepted for publication in The Journal of Infectious Diseases following peer review. The version of record Yiyao Huang, Ahmed Abdelgawad, Andrey Turchinovich, Suzanne Queen, Celina Monteiro Abreu, Xianming Zhu, Mona Batish, Lei Zheng, Kenneth W Witwer, RNA Landscapes of Brain and Brain-Derived Extracellular Vesicles in Simian Immunodeficiency Virus Infection and Central Nervous System Pathology, The Journal of Infectious Diseases, 2023;, jiad563, https://doi.org/10.1093/infdis/jiad563 is available online at: https://doi.org/10.1093/infdis/jiad563. © The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. This article will be embargoed until 12/11/2024.
Keywords
SIV, HIV, HAND, extracellular vesicles, bdEVs, miRNAs, mRNAs, circRNAs, exosomes, ectosomes
Citation
Yiyao Huang, Ahmed Abdelgawad, Andrey Turchinovich, Suzanne Queen, Celina Monteiro Abreu, Xianming Zhu, Mona Batish, Lei Zheng, Kenneth W Witwer, RNA Landscapes of Brain and Brain-Derived Extracellular Vesicles in Simian Immunodeficiency Virus Infection and Central Nervous System Pathology, The Journal of Infectious Diseases, 2023;, jiad563, https://doi.org/10.1093/infdis/jiad563