RNA Landscapes of Brain and Brain-Derived Extracellular Vesicles in Simian Immunodeficiency Virus Infection and Central Nervous System Pathology
| Author(s) | Huang, Yiyao | |
| Author(s) | Abdelgawad, Ahmed | |
| Author(s) | Turchinovich, Andrey | |
| Author(s) | Queen, Suzanne | |
| Author(s) | Abreu, Celina Monteiro | |
| Author(s) | Zhu, Xianming | |
| Author(s) | Batish, Mona | |
| Author(s) | Zheng, Lei | |
| Author(s) | Witwer, Kenneth W. | |
| Date Accessioned | 2024-02-29T20:34:05Z | |
| Date Available | 2024-02-29T20:34:05Z | |
| Publication Date | 2023-12-11 | |
| 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. | |
| 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. | |
| Sponsor | This work was supported by the National Institutes of Health (NIH), National Institute on Drug Abuse (grant numbers DA040385 and DA047807 to K. W. W.); by 2 pilot grants awarded to Y. H. through the Johns Hopkins National Institute of Mental Health (NIMH) Center (supported by National Institute of Mental Health MH075673) and the Johns Hopkins University Center for AIDS Research (supported by National Institutes of Health/National Institute of Allergy and Infectious Diseases P30AI094189-01A1); and the National Science Foundation (grant number 2244127 to M. B.). The Witwer laboratory is also supported in part by National Cancer Institute/Common Fund (grant number CA241694); National Institute of Allergy and Infectious Diseases (grant number AI144997); National Institute of Mental Health (NIMH) (grant number MH118164); and the Johns Hopkins University Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease. Samples used in this study were derived in part from research supported by National Institutes of Health (NIH) (grant number U42OD013117 to Johns Hopkins pigtailed macaque breeding colony); National Institute of Neurological Disorders and Stroke (grant number NS089482 to Joseph L. Mankowski); and National Institute of Mental Health (NIMH) (grant number MH070306 to Janice E. Clements). | |
| 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 | |
| ISSN | 1537-6613 | |
| URL | https://udspace.udel.edu/handle/19716/34085 | |
| Language | en_US | |
| Publisher | The Journal of Infectious Diseases | |
| Keywords | SIV | |
| Keywords | HIV | |
| Keywords | HAND | |
| Keywords | extracellular vesicles | |
| Keywords | bdEVs | |
| Keywords | miRNAs | |
| Keywords | mRNAs | |
| Keywords | circRNAs | |
| Keywords | exosomes | |
| Keywords | ectosomes | |
| Title | RNA Landscapes of Brain and Brain-Derived Extracellular Vesicles in Simian Immunodeficiency Virus Infection and Central Nervous System Pathology | |
| Type | Article |
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