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The Proteome and Secretome of Cortical Brain Cells Infected With Herpes Simplex Virus

Infections of the brain with herpes simplex virus type 1 (HSV-1) cause life-threatening Herpes simplex encephalitis (HSE) characterized by viral replication in neurons and neuro-inflammation including an infiltration of peripheral immune cells. HSV-1 reprograms host cells to foster its own replicati...

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Autores principales: Hensel, Niko, Raker, Verena, Förthmann, Benjamin, Buch, Anna, Sodeik, Beate, Pich, Andreas, Claus, Peter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481480/
https://www.ncbi.nlm.nih.gov/pubmed/32973653
http://dx.doi.org/10.3389/fneur.2020.00844
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author Hensel, Niko
Raker, Verena
Förthmann, Benjamin
Buch, Anna
Sodeik, Beate
Pich, Andreas
Claus, Peter
author_facet Hensel, Niko
Raker, Verena
Förthmann, Benjamin
Buch, Anna
Sodeik, Beate
Pich, Andreas
Claus, Peter
author_sort Hensel, Niko
collection PubMed
description Infections of the brain with herpes simplex virus type 1 (HSV-1) cause life-threatening Herpes simplex encephalitis (HSE) characterized by viral replication in neurons and neuro-inflammation including an infiltration of peripheral immune cells. HSV-1 reprograms host cells to foster its own replication and for immune evasion, but eventually the immune responses clear the infection in most patients. However, many survivors suffer from long-term neuronal damage and cannot regenerate all brain functions. HSV-1 influences the physiology of neurons, astrocytes, oligodendrocytes and microglia, and significantly changes their protein expression and secretion pattern. To characterize temporal changes upon HSV-1 infection in detail, we inoculated mixed primary cultures of the murine brain cortex, and performed quantitative mass spectrometry analyses of the cell-associated proteome and the secretome. We identified 28 differentially regulated host proteins influencing inflammasome formation and intracellular vesicle trafficking during endocytosis and secretion. The NIMA-related kinase 7 (NEK7), a critical component of the inflammasome, and ArfGap1, a regulator of endocytosis, were significantly up-regulated upon HSV-1 infection. In the secretome, we identified 71 proteins including guidance cues regulating axonal regeneration, such as semaphorin6D, which were enriched in the conditioned media of HSV-1 infected cells. Modulation of inflammasome activity and intracellular membrane traffic are critical for HSV-1 cell entry, virus assembly, and intracellular spread. Our proteome analysis provides first clues on host factors that might dampen the inflammasome response and modulate intracellular vesicle transport to promote HSV infection of the brain. Furthermore, our secretome analysis revealed a set of proteins involved in neuroregeneration that might foster neuronal repair processes to restore brain functions after clearance of an HSV-1 infection.
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spelling pubmed-74814802020-09-23 The Proteome and Secretome of Cortical Brain Cells Infected With Herpes Simplex Virus Hensel, Niko Raker, Verena Förthmann, Benjamin Buch, Anna Sodeik, Beate Pich, Andreas Claus, Peter Front Neurol Neurology Infections of the brain with herpes simplex virus type 1 (HSV-1) cause life-threatening Herpes simplex encephalitis (HSE) characterized by viral replication in neurons and neuro-inflammation including an infiltration of peripheral immune cells. HSV-1 reprograms host cells to foster its own replication and for immune evasion, but eventually the immune responses clear the infection in most patients. However, many survivors suffer from long-term neuronal damage and cannot regenerate all brain functions. HSV-1 influences the physiology of neurons, astrocytes, oligodendrocytes and microglia, and significantly changes their protein expression and secretion pattern. To characterize temporal changes upon HSV-1 infection in detail, we inoculated mixed primary cultures of the murine brain cortex, and performed quantitative mass spectrometry analyses of the cell-associated proteome and the secretome. We identified 28 differentially regulated host proteins influencing inflammasome formation and intracellular vesicle trafficking during endocytosis and secretion. The NIMA-related kinase 7 (NEK7), a critical component of the inflammasome, and ArfGap1, a regulator of endocytosis, were significantly up-regulated upon HSV-1 infection. In the secretome, we identified 71 proteins including guidance cues regulating axonal regeneration, such as semaphorin6D, which were enriched in the conditioned media of HSV-1 infected cells. Modulation of inflammasome activity and intracellular membrane traffic are critical for HSV-1 cell entry, virus assembly, and intracellular spread. Our proteome analysis provides first clues on host factors that might dampen the inflammasome response and modulate intracellular vesicle transport to promote HSV infection of the brain. Furthermore, our secretome analysis revealed a set of proteins involved in neuroregeneration that might foster neuronal repair processes to restore brain functions after clearance of an HSV-1 infection. Frontiers Media S.A. 2020-08-27 /pmc/articles/PMC7481480/ /pubmed/32973653 http://dx.doi.org/10.3389/fneur.2020.00844 Text en Copyright © 2020 Hensel, Raker, Förthmann, Buch, Sodeik, Pich and Claus. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neurology
Hensel, Niko
Raker, Verena
Förthmann, Benjamin
Buch, Anna
Sodeik, Beate
Pich, Andreas
Claus, Peter
The Proteome and Secretome of Cortical Brain Cells Infected With Herpes Simplex Virus
title The Proteome and Secretome of Cortical Brain Cells Infected With Herpes Simplex Virus
title_full The Proteome and Secretome of Cortical Brain Cells Infected With Herpes Simplex Virus
title_fullStr The Proteome and Secretome of Cortical Brain Cells Infected With Herpes Simplex Virus
title_full_unstemmed The Proteome and Secretome of Cortical Brain Cells Infected With Herpes Simplex Virus
title_short The Proteome and Secretome of Cortical Brain Cells Infected With Herpes Simplex Virus
title_sort proteome and secretome of cortical brain cells infected with herpes simplex virus
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481480/
https://www.ncbi.nlm.nih.gov/pubmed/32973653
http://dx.doi.org/10.3389/fneur.2020.00844
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