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Tytuł pozycji:

Small RNA sequencing of extracellular vesicles identifies circulating miRNAs related to inflammation and oxidative stress in HIV patients

Tytuł:
Small RNA sequencing of extracellular vesicles identifies circulating miRNAs related to inflammation and oxidative stress in HIV patients
Autorzy:
Sukrutha Chettimada
David R. Lorenz
Vikas Misra
Steven M. Wolinsky
Dana Gabuzda
Temat:
Small RNA
MiRNA
Extracellular vesicles
Exosomes
HIV
Inflammation
Immunologic diseases. Allergy
RC581-607
Źródło:
BMC Immunology, Vol 21, Iss 1, Pp 1-20 (2020)
Wydawca:
BMC, 2020.
Rok publikacji:
2020
Kolekcja:
LCC:Immunologic diseases. Allergy
Typ dokumentu:
article
Opis pliku:
electronic resource
Język:
English
ISSN:
1471-2172
Relacje:
http://link.springer.com/article/10.1186/s12865-020-00386-5; https://doaj.org/toc/1471-2172
DOI:
10.1186/s12865-020-00386-5
Dostęp URL:
https://doaj.org/article/71e10c22bd3141429ae074cee76d1682  Link otwiera się w nowym oknie
Numer akcesji:
edsdoj.71e10c22bd3141429ae074cee76d1682
Czasopismo naukowe
Abstract Background Extracellular vesicles (EVs) are nano-sized particles secreted by most cells. EVs carry nucleic acids that hold promise as potential biomarkers in various diseases. Human immunodeficiency virus type 1 (HIV) infects CD4+ T cells and induces immune dysfunction, inflammation, and EV secretion, but little is known about EV small RNA cargo in relation to immune dysregulation in HIV-infected individuals. Here, we characterize small RNA carried by circulating EVs in HIV-positive subjects on antiretroviral therapy (ART) relative to uninfected controls by next-generation RNA sequencing. Results Plasma EVs isolated from HIV-positive and HIV-negative subjects in test (n = 24) and validation (n = 16) cohorts were characterized by electron microscopy, nanoparticle tracking analysis, and immunoblotting for exosome markers. EVs were more abundant in plasma from HIV-positive compared to HIV-negative subjects. Small RNA sequencing of plasma EVs in the test cohort identified diverse small RNA species including miRNA, piRNA, snRNA, snoRNA, tRNA, and rRNA, with miRNA being the most abundant. A total of 351 different miRNAs were detected in plasma EVs, with the top 50 miRNAs accounting for 90% of all miRNA reads. miR-26a-5p was the most abundant miRNA, followed by miR-21-5p and miR-148-3p. qRT-PCR analysis showed that six miRNAs (miR-10a-5p, − 21-5p, −27b-3p, − 122-5p, −146a-5p, − 423-5p) were significantly increased in plasma EVs from HIV-positive compared to HIV-negative subjects in the validation cohort. Furthermore, miR-21-5p, −27b-3p, −146a-5p, and − 423-5p correlated positively with metabolite markers of oxidative stress and negatively with anti-inflammatory polyunsaturated fatty acids. Over-representation and pathway enrichment analyses of miRNAs and their target genes predicted functional association with oxidative stress responses, interferon gamma signaling, Toll-like receptor signaling, TGF beta signaling, and Notch signaling. Conclusions HIV-positive individuals on ART have increased abundance of circulating EVs carrying diverse small RNAs, with miRNAs being the most abundant. Several miRNAs associated with inflammation and oxidative stress are increased in circulating EVs of HIV-positive individuals, representing potential biomarkers of targetable pathways that contribute to disease pathogenesis.
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