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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Main Authors: Anikó Kun-Varga, Barbara Gubán, Vanda Miklós, Shahram Parvaneh, Melinda Guba, Diána Szűcs, Tamás Monostori, János Varga, Ákos Varga, Zsolt Rázga, Zsuzsanna Bata-Csörgő, Lajos Kemény, Klára Megyeri, Zoltán Veréb
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/24/15/11989
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author Anikó Kun-Varga
Barbara Gubán
Vanda Miklós
Shahram Parvaneh
Melinda Guba
Diána Szűcs
Tamás Monostori
János Varga
Ákos Varga
Zsolt Rázga
Zsuzsanna Bata-Csörgő
Lajos Kemény
Klára Megyeri
Zoltán Veréb
author_facet Anikó Kun-Varga
Barbara Gubán
Vanda Miklós
Shahram Parvaneh
Melinda Guba
Diána Szűcs
Tamás Monostori
János Varga
Ákos Varga
Zsolt Rázga
Zsuzsanna Bata-Csörgő
Lajos Kemény
Klára Megyeri
Zoltán Veréb
author_sort Anikó Kun-Varga
collection DOAJ
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 doaj.art-0dbced969cd545a89c185aa1b9c0993e2023-11-18T22:58:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-07-0124151198910.3390/ijms241511989Herpes Simplex Virus Infection Alters the Immunological Properties of Adipose-Tissue-Derived Mesenchymal-Stem CellsAnikó Kun-Varga0Barbara Gubán1Vanda Miklós2Shahram Parvaneh3Melinda Guba4Diána Szűcs5Tamás Monostori6János Varga7Ákos Varga8Zsolt Rázga9Zsuzsanna Bata-Csörgő10Lajos Kemény11Klára Megyeri12Zoltán Veréb13Regenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, HungaryRegenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, HungaryBiobank, University of Szeged, H-6720 Szeged, HungaryHCEMM-SZTE Skin Research Group, University of Szeged, H-6720 Szeged, HungaryRegenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, HungaryRegenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, HungaryRegenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, HungaryDermatosurgery and Plastic Surgery Unit, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, HungaryDermatosurgery and Plastic Surgery Unit, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, HungaryDepartment of Pathology, University of Szeged, H-6720 Szeged, HungaryHCEMM-SZTE Skin Research Group, University of Szeged, H-6720 Szeged, HungaryRegenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, HungaryDepartment of Medical Microbiology, University of Szeged, H-6720 Szeged, HungaryRegenerative Medicine and Cellular Pharmacology Laboratory, Department of Dermatology and Allergology, University of Szeged, H-6720 Szeged, HungaryThe 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.https://www.mdpi.com/1422-0067/24/15/11989adipose-derived mesenchymal stem cellsinflammationgene expression
spellingShingle Anikó Kun-Varga
Barbara Gubán
Vanda Miklós
Shahram Parvaneh
Melinda Guba
Diána Szűcs
Tamás Monostori
János Varga
Ákos Varga
Zsolt Rázga
Zsuzsanna Bata-Csörgő
Lajos Kemény
Klára Megyeri
Zoltán Veréb
Herpes Simplex Virus Infection Alters the Immunological Properties of Adipose-Tissue-Derived Mesenchymal-Stem Cells
International Journal of Molecular Sciences
adipose-derived mesenchymal stem cells
inflammation
gene expression
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 adipose-derived mesenchymal stem cells
inflammation
gene expression
url https://www.mdpi.com/1422-0067/24/15/11989
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