miRNA profiling of primate cervicovaginal lavage and extracellular vesicles reveals miR-186-5p as a potential antiretroviral factor in macrophages.
Animals
Biomarkers
/ metabolism
Cervix Uteri
/ metabolism
Extracellular Vesicles
/ genetics
Female
Gene Expression
/ genetics
Gene Expression Profiling
/ methods
Gene Expression Regulation
/ genetics
HIV Infections
/ genetics
Macaca mulatta
Macrophages
/ metabolism
Menstrual Cycle
/ genetics
MicroRNAs
/ analysis
Primates
/ genetics
Simian Acquired Immunodeficiency Syndrome
/ genetics
Simian Immunodeficiency Virus
/ pathogenicity
Transcriptome
/ genetics
Vagina
/ metabolism
Vaginal Douching
/ methods
HIV‐1
cervicovaginal lavage
exosome
extracellular vesicle
microRNA
Journal
FEBS open bio
ISSN: 2211-5463
Titre abrégé: FEBS Open Bio
Pays: England
ID NLM: 101580716
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
02
12
2019
revised:
03
06
2020
accepted:
13
08
2020
entrez:
5
10
2020
pubmed:
6
10
2020
medline:
24
11
2021
Statut:
ppublish
Résumé
Cervicovaginal secretions, or their components collected, are referred to as cervicovaginal lavage (CVL). CVL constituents have utility as biomarkers and play protective roles in wound healing and against HIV-1 infection. However, several components of cervicovaginal fluids are less well understood, such as extracellular RNAs and their carriers, for example, extracellular vesicles (EVs). EVs comprise a wide array of double-leaflet membrane extracellular particles and range in diameter from 30 nm to over one micron. The aim of this study was to determine whether differentially regulated CVL microRNAs (miRNAs) might influence retrovirus replication. To this end, we characterized EVs and miRNAs of primate CVL during the menstrual cycle and simian immunodeficiency virus (SIV) infection of macaques. EVs were enriched by stepped ultracentrifugation, and miRNA profiles were assessed with a medium-throughput stem-loop/hydrolysis probe qPCR platform. Whereas hormone cycling was abnormal in infected subjects, EV concentration correlated with progesterone concentration in uninfected subjects. miRNAs were present predominantly in the EV-depleted CVL supernatant. Only a small number of CVL miRNAs changed during the menstrual cycle or SIV infection, for example, miR-186-5p, which was depleted in retroviral infection. This miRNA inhibited HIV replication in infected macrophages in vitro. In silico target prediction and pathway enrichment analyses shed light on the probable functions of miR-186-5p in hindering HIV infections via immunoregulation, T-cell regulation, disruption of viral pathways, etc. These results provide further evidence for the potential of EVs and small RNAs as biomarkers or effectors of disease processes in the reproductive tract.
Identifiants
pubmed: 33017084
doi: 10.1002/2211-5463.12952
pmc: PMC7530394
doi:
Substances chimiques
Biomarkers
0
MIRN186 microRNA, human
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2021-2039Subventions
Organisme : NIH HHS
ID : U42 OD013117
Pays : United States
Organisme : NIMH NIH HHS
ID : R21 MH118164
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA047807
Pays : United States
Organisme : NCI NIH HHS
ID : UG3 CA241694
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI144997
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA040385
Pays : United States
Organisme : NIH HHS
ID : T32 OD011089
Pays : United States
Informations de copyright
© 2020 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
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