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Herpes Simplex Virus Infection Alters the Immunological Properties of Adipose-Tissue-Derived Mesenchymal-Stem Cells

The proper functioning of mesenchymal stem cells (MSCs) is of paramount importance for the homeostasis of the body. Inflammation and infection can alter the function of MSCs, which can also affect the regenerative potential and immunological status of tissues. It is not known whether human herpes si...

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Autores principales: Kun-Varga, Anikó, Gubán, Barbara, Miklós, Vanda, Parvaneh, Shahram, Guba, Melinda, Szűcs, Diána, Monostori, Tamás, Varga, János, Varga, Ákos, Rázga, Zsolt, Bata-Csörgő, Zsuzsanna, Kemény, Lajos, Megyeri, Klára, Veréb, Zoltán
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418794/
https://www.ncbi.nlm.nih.gov/pubmed/37569367
http://dx.doi.org/10.3390/ijms241511989
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author Kun-Varga, Anikó
Gubán, Barbara
Miklós, Vanda
Parvaneh, Shahram
Guba, Melinda
Szűcs, Diána
Monostori, Tamás
Varga, János
Varga, Ákos
Rázga, Zsolt
Bata-Csörgő, Zsuzsanna
Kemény, Lajos
Megyeri, Klára
Veréb, Zoltán
author_facet Kun-Varga, Anikó
Gubán, Barbara
Miklós, Vanda
Parvaneh, Shahram
Guba, Melinda
Szűcs, Diána
Monostori, Tamás
Varga, János
Varga, Ákos
Rázga, Zsolt
Bata-Csörgő, Zsuzsanna
Kemény, Lajos
Megyeri, Klára
Veréb, Zoltán
author_sort Kun-Varga, Anikó
collection PubMed
description The proper functioning of mesenchymal stem cells (MSCs) is of paramount importance for the homeostasis of the body. Inflammation and infection can alter the function of MSCs, which can also affect the regenerative potential and immunological status of tissues. It is not known whether human herpes simplex viruses 1 and 2 (HSV1 and HSV2), well-known human pathogens that can cause lifelong infections, can induce changes in MSCs. In non-healing ulcers, HSV infection is known to affect deeper tissue layers. In addition, HSV infection can recur after initially successful cell therapies. Our aim was to study the response of adipose-derived MSCs (ADMSCs) to HSV infection in vitro. After confirming the phenotype and differentiation capacity of the isolated cells, we infected the cells in vitro with HSV1-KOS, HSV1-532 and HSV2 virus strains. Twenty-four hours after infection, we examined the gene expression of the cells via RNA-seq and RT-PCR; detected secreted cytokines via protein array; and determined autophagy via Western blot, transmission electron microscopy (TEM) and fluorescence microscopy. Infection with different HSV strains resulted in different gene-expression patterns. In addition to the activation of pathways characteristic of viral infections, distinct non-immunological pathways (autophagy, tissue regeneration and differentiation) were also activated according to analyses with QIAGEN Ingenuity Pathway Analysis, Kyoto Encyclopedia of Genes and Genome and Genome Ontology Enrichment. Viral infections increased autophagy, as confirmed via TEM image analysis, and also increased levels of the microtubule-associated protein light chain 3 (LC3B) II protein. We identified significantly altered accumulation for 16 cytokines involved in tissue regeneration and inflammation. Our studies demonstrated that HSV infection can alter the viability and immunological status of ADMSCs, which may have implications for ADMSC-based cell therapies. Alterations in autophagy can affect numerous processes in MSCs, including the inhibition of tissue regeneration as well as pathological differentiation.
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spelling pubmed-104187942023-08-12 Herpes Simplex Virus Infection Alters the Immunological Properties of Adipose-Tissue-Derived Mesenchymal-Stem Cells Kun-Varga, Anikó Gubán, Barbara Miklós, Vanda Parvaneh, Shahram Guba, Melinda Szűcs, Diána Monostori, Tamás Varga, János Varga, Ákos Rázga, Zsolt Bata-Csörgő, Zsuzsanna Kemény, Lajos Megyeri, Klára Veréb, Zoltán Int J Mol Sci Article The proper functioning of mesenchymal stem cells (MSCs) is of paramount importance for the homeostasis of the body. Inflammation and infection can alter the function of MSCs, which can also affect the regenerative potential and immunological status of tissues. It is not known whether human herpes simplex viruses 1 and 2 (HSV1 and HSV2), well-known human pathogens that can cause lifelong infections, can induce changes in MSCs. In non-healing ulcers, HSV infection is known to affect deeper tissue layers. In addition, HSV infection can recur after initially successful cell therapies. Our aim was to study the response of adipose-derived MSCs (ADMSCs) to HSV infection in vitro. After confirming the phenotype and differentiation capacity of the isolated cells, we infected the cells in vitro with HSV1-KOS, HSV1-532 and HSV2 virus strains. Twenty-four hours after infection, we examined the gene expression of the cells via RNA-seq and RT-PCR; detected secreted cytokines via protein array; and determined autophagy via Western blot, transmission electron microscopy (TEM) and fluorescence microscopy. Infection with different HSV strains resulted in different gene-expression patterns. In addition to the activation of pathways characteristic of viral infections, distinct non-immunological pathways (autophagy, tissue regeneration and differentiation) were also activated according to analyses with QIAGEN Ingenuity Pathway Analysis, Kyoto Encyclopedia of Genes and Genome and Genome Ontology Enrichment. Viral infections increased autophagy, as confirmed via TEM image analysis, and also increased levels of the microtubule-associated protein light chain 3 (LC3B) II protein. We identified significantly altered accumulation for 16 cytokines involved in tissue regeneration and inflammation. Our studies demonstrated that HSV infection can alter the viability and immunological status of ADMSCs, which may have implications for ADMSC-based cell therapies. Alterations in autophagy can affect numerous processes in MSCs, including the inhibition of tissue regeneration as well as pathological differentiation. MDPI 2023-07-26 /pmc/articles/PMC10418794/ /pubmed/37569367 http://dx.doi.org/10.3390/ijms241511989 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Kun-Varga, Anikó
Gubán, Barbara
Miklós, Vanda
Parvaneh, Shahram
Guba, Melinda
Szűcs, Diána
Monostori, Tamás
Varga, János
Varga, Ákos
Rázga, Zsolt
Bata-Csörgő, Zsuzsanna
Kemény, Lajos
Megyeri, Klára
Veréb, Zoltán
Herpes Simplex Virus Infection Alters the Immunological Properties of Adipose-Tissue-Derived Mesenchymal-Stem Cells
title Herpes Simplex Virus Infection Alters the Immunological Properties of Adipose-Tissue-Derived Mesenchymal-Stem Cells
title_full Herpes Simplex Virus Infection Alters the Immunological Properties of Adipose-Tissue-Derived Mesenchymal-Stem Cells
title_fullStr Herpes Simplex Virus Infection Alters the Immunological Properties of Adipose-Tissue-Derived Mesenchymal-Stem Cells
title_full_unstemmed Herpes Simplex Virus Infection Alters the Immunological Properties of Adipose-Tissue-Derived Mesenchymal-Stem Cells
title_short Herpes Simplex Virus Infection Alters the Immunological Properties of Adipose-Tissue-Derived Mesenchymal-Stem Cells
title_sort herpes simplex virus infection alters the immunological properties of adipose-tissue-derived mesenchymal-stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10418794/
https://www.ncbi.nlm.nih.gov/pubmed/37569367
http://dx.doi.org/10.3390/ijms241511989
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