JC Polyomavirus Modifies the Expression of Human MicroRNAs in Progressive Multifocal Leukoencephalopathy Brain

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2023 Mar 29

PMID 36988117

Authors

Anni Honkimaa

Joni Suppula

Olli Tynninen

Mika Saarela

Hanna Liimatainen

Pia Laine

Petri Auvinen

Eeva Auvinen

Affiliations

Soon will be listed here.

Abstract

Progressive multifocal leukoencephalopathy (PML) is a severe neurological condition caused by reactivation of JC polyomavirus (JCPyV) in immunosuppression. Asymptomatic JCPyV persists in peripheral tissues. Upon reactivation, neurotropic rearrangements may emerge, and the virus gains access to the brain. To assess the mechanisms of PML pathogenesis, brain tissue material from PML patients was collected for small RNA sequencing. Upregulation of 8 microRNAs (miRNAs) in PML brain was validated using quantitative microRNA polymerase chain reaction (PCR). Bioinformatics tools were utilized to identify major associations of the upregulated miRNAs: neuroinflammation and blood-brain barrier disruption. The results indicate involvement of human miRNA regulation in PML pathogenesis.

Citing Articles

Exploring JC Polyomavirus Sequences and Human Gene Expression in Brain Tissue of Patients With Progressive Multifocal Leukoencephalopathy.

Honkimaa A, Laine P, Suppula J, Tynninen O, Saarela M, Laakso S J Infect Dis. 2024; 230(3):e732-e736.

PMID: 38365889 PMC: 11420775. DOI: 10.1093/infdis/jiae066.

References

Kartau M, Sipila J, Auvinen E, Palomaki M, Verkkoniemi-Ahola A . Progressive Multifocal Leukoencephalopathy: Current Insights. Degener Neurol Neuromuscul Dis. 2019; 9:109-121. PMC: 6896915. DOI: 10.2147/DNND.S203405. View

Takahashi K, Sato Y, Sekizuka T, Kuroda M, Suzuki T, Hasegawa H . High expression of JC polyomavirus-encoded microRNAs in progressive multifocal leukoencephalopathy tissues and its repressive role in virus replication. PLoS Pathog. 2020; 16(4):e1008523. PMC: 7200015. DOI: 10.1371/journal.ppat.1008523. View

Morris-Love J, Gee G, OHara B, Assetta B, Atkinson A, Dugan A . JC Polyomavirus Uses Extracellular Vesicles To Infect Target Cells. mBio. 2019; 10(2). PMC: 6456752. DOI: 10.1128/mBio.00379-19. View

Wollebo H, White M, Gordon J, Berger J, Khalili K . Persistence and pathogenesis of the neurotropic polyomavirus JC. Ann Neurol. 2015; 77(4):560-70. PMC: 4376594. DOI: 10.1002/ana.24371. View

Ge X, Li W, Huang S, Yin Z, Yang M, Han Z . Increased miR-21-3p in Injured Brain Microvascular Endothelial Cells after Traumatic Brain Injury Aggravates Blood-Brain Barrier Damage by Promoting Cellular Apoptosis and Inflammation through Targeting MAT2B. J Neurotrauma. 2018; 36(8):1291-1305. DOI: 10.1089/neu.2018.5728. View

Lopez-Ramirez M, Wu D, Pryce G, Simpson J, Reijerkerk A, King-Robson J . MicroRNA-155 negatively affects blood-brain barrier function during neuroinflammation. FASEB J. 2014; 28(6):2551-65. DOI: 10.1096/fj.13-248880. View

Jafarzadeh A, Naseri A, Shojaie L, Nemati M, Jafarzadeh S, Baghi H . MicroRNA-155 and antiviral immune responses. Int Immunopharmacol. 2021; 101(Pt A):108188. DOI: 10.1016/j.intimp.2021.108188. View

Ingwersen J, Menge T, Wingerath B, Kaya D, Graf J, Prozorovski T . Natalizumab restores aberrant miRNA expression profile in multiple sclerosis and reveals a critical role for miR-20b. Ann Clin Transl Neurol. 2015; 2(1):43-55. PMC: 4301674. DOI: 10.1002/acn3.152. View

Maciak K, Dziedzic A, Miller E, Saluk-Bijak J . miR-155 as an Important Regulator of Multiple Sclerosis Pathogenesis. A Review. Int J Mol Sci. 2021; 22(9). PMC: 8122504. DOI: 10.3390/ijms22094332. View

10.

Mandolesi G, Vito F, Musella A, Gentile A, Bullitta S, Fresegna D . miR-142-3p Is a Key Regulator of IL-1β-Dependent Synaptopathy in Neuroinflammation. J Neurosci. 2017; 37(3):546-561. PMC: 6596761. DOI: 10.1523/JNEUROSCI.0851-16.2016. View

11.

Juzwik C, Drake S, Zhang Y, Paradis-Isler N, Sylvester A, Amar-Zifkin A . microRNA dysregulation in neurodegenerative diseases: A systematic review. Prog Neurobiol. 2019; 182:101664. DOI: 10.1016/j.pneurobio.2019.101664. View

12.

Ravichandran V, Major E . DNA-binding transcription factor NF-1A negatively regulates JC virus multiplication. J Gen Virol. 2008; 89(Pt 6):1396-1401. PMC: 2701216. DOI: 10.1099/vir.0.2008/000059-0. View

13.

Sievers C, Meira M, Hoffmann F, Fontoura P, Kappos L, Lindberg R . Altered microRNA expression in B lymphocytes in multiple sclerosis: towards a better understanding of treatment effects. Clin Immunol. 2012; 144(1):70-9. DOI: 10.1016/j.clim.2012.04.002. View

14.

Gaudet A, Fonken L, Watkins L, Nelson R, Popovich P . MicroRNAs: Roles in Regulating Neuroinflammation. Neuroscientist. 2017; 24(3):221-245. PMC: 8377730. DOI: 10.1177/1073858417721150. View

15.

Bai X, Bian Z . MicroRNA-21 Is a Versatile Regulator and Potential Treatment Target in Central Nervous System Disorders. Front Mol Neurosci. 2022; 15:842288. PMC: 8841607. DOI: 10.3389/fnmol.2022.842288. View