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HHV-6A infection induces amyloid-beta expression and activation of microglial cells

BACKGROUND: The control of viral infections in the brain involves the activation of microglial cells, the macrophages of the brain that are constantly surveying the central nervous system, and the production of amyloid-beta (Aβ) as an anti-microbial molecule. Recent findings suggest a possible impli...

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Autores principales: Bortolotti, Daria, Gentili, Valentina, Rotola, Antonella, Caselli, Elisabetta, Rizzo, Roberta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909659/
https://www.ncbi.nlm.nih.gov/pubmed/31831060
http://dx.doi.org/10.1186/s13195-019-0552-6
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author Bortolotti, Daria
Gentili, Valentina
Rotola, Antonella
Caselli, Elisabetta
Rizzo, Roberta
author_facet Bortolotti, Daria
Gentili, Valentina
Rotola, Antonella
Caselli, Elisabetta
Rizzo, Roberta
author_sort Bortolotti, Daria
collection PubMed
description BACKGROUND: The control of viral infections in the brain involves the activation of microglial cells, the macrophages of the brain that are constantly surveying the central nervous system, and the production of amyloid-beta (Aβ) as an anti-microbial molecule. Recent findings suggest a possible implication of HHV-6A in AD. We evaluated the effect of HHV-6A infection on microglial cell expression Aβ and the activation status, determined by TREM2, ApoE, cytokines, and tau expression. METHODS: We have infected microglial cells (HMC3, ATCC®CRL-3304), in monolayer and human peripheral blood monocyte-derived microglia (PBM-microglia) spheroid 3D model, with HHV-6A (strain U1102) cell-free virus inocula with 100 genome equivalents per 1 cell. We collected the cells 1, 3, 7, and 14 days post-infection (d.p.i.) and analyzed them for viral DNA and RNA, ApoE, Aβ (1-40, 1-42), tau, and phospho-tau (Threonine 181) by real-time immunofluorescence and cytokines by immunoenzymatic assay. RESULTS: We observed a productive infection by HHV-6A. The expression of Aβ 1-42 increased from 3 d.p.i., while no significant induction was observed for Aβ 1-40. The HHV-6A infection induced the activation (TREM2, IL-1beta, ApoE) and migration of microglial cells. The secretion of tau started from 7 d.p.i., with an increasing percentage of the phosphorylated form. CONCLUSIONS: In conclusion, microglial cells are permissive to HHV-6A infection that induces the expression of Aβ and an activation status. Meanwhile, we hypothesize a paracrine effect of HHV-6A infection that activates and induces microglia migration to the site of infection.
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spelling pubmed-69096592019-12-30 HHV-6A infection induces amyloid-beta expression and activation of microglial cells Bortolotti, Daria Gentili, Valentina Rotola, Antonella Caselli, Elisabetta Rizzo, Roberta Alzheimers Res Ther Research BACKGROUND: The control of viral infections in the brain involves the activation of microglial cells, the macrophages of the brain that are constantly surveying the central nervous system, and the production of amyloid-beta (Aβ) as an anti-microbial molecule. Recent findings suggest a possible implication of HHV-6A in AD. We evaluated the effect of HHV-6A infection on microglial cell expression Aβ and the activation status, determined by TREM2, ApoE, cytokines, and tau expression. METHODS: We have infected microglial cells (HMC3, ATCC®CRL-3304), in monolayer and human peripheral blood monocyte-derived microglia (PBM-microglia) spheroid 3D model, with HHV-6A (strain U1102) cell-free virus inocula with 100 genome equivalents per 1 cell. We collected the cells 1, 3, 7, and 14 days post-infection (d.p.i.) and analyzed them for viral DNA and RNA, ApoE, Aβ (1-40, 1-42), tau, and phospho-tau (Threonine 181) by real-time immunofluorescence and cytokines by immunoenzymatic assay. RESULTS: We observed a productive infection by HHV-6A. The expression of Aβ 1-42 increased from 3 d.p.i., while no significant induction was observed for Aβ 1-40. The HHV-6A infection induced the activation (TREM2, IL-1beta, ApoE) and migration of microglial cells. The secretion of tau started from 7 d.p.i., with an increasing percentage of the phosphorylated form. CONCLUSIONS: In conclusion, microglial cells are permissive to HHV-6A infection that induces the expression of Aβ and an activation status. Meanwhile, we hypothesize a paracrine effect of HHV-6A infection that activates and induces microglia migration to the site of infection. BioMed Central 2019-12-12 /pmc/articles/PMC6909659/ /pubmed/31831060 http://dx.doi.org/10.1186/s13195-019-0552-6 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bortolotti, Daria
Gentili, Valentina
Rotola, Antonella
Caselli, Elisabetta
Rizzo, Roberta
HHV-6A infection induces amyloid-beta expression and activation of microglial cells
title HHV-6A infection induces amyloid-beta expression and activation of microglial cells
title_full HHV-6A infection induces amyloid-beta expression and activation of microglial cells
title_fullStr HHV-6A infection induces amyloid-beta expression and activation of microglial cells
title_full_unstemmed HHV-6A infection induces amyloid-beta expression and activation of microglial cells
title_short HHV-6A infection induces amyloid-beta expression and activation of microglial cells
title_sort hhv-6a infection induces amyloid-beta expression and activation of microglial cells
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909659/
https://www.ncbi.nlm.nih.gov/pubmed/31831060
http://dx.doi.org/10.1186/s13195-019-0552-6
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