Coinfection of Dermal Fibroblasts by Human Cytomegalovirus and Human Herpesvirus 6 Can Boost the Expression of Fibrosis-Associated MicroRNAs

Tissue fibrosis can affect every type of tissue or organ, often leading to organ malfunction; however, the mechanisms involved in this process are not yet clarified. A role has been hypothesized for Human Cytomegalovirus (HCMV) and Human Herpesvirus 6 (HHV-6) infections as triggers of systemic scler...

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Main Authors: Irene Soffritti, Maria D’Accolti, Clara Maccari, Francesca Bini, Eleonora Mazziga, Maria-Cristina Arcangeletti, Elisabetta Caselli
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Microorganisms
Subjects:
Online Access:https://www.mdpi.com/2076-2607/11/2/412
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author Irene Soffritti
Maria D’Accolti
Clara Maccari
Francesca Bini
Eleonora Mazziga
Maria-Cristina Arcangeletti
Elisabetta Caselli
author_facet Irene Soffritti
Maria D’Accolti
Clara Maccari
Francesca Bini
Eleonora Mazziga
Maria-Cristina Arcangeletti
Elisabetta Caselli
author_sort Irene Soffritti
collection DOAJ
description Tissue fibrosis can affect every type of tissue or organ, often leading to organ malfunction; however, the mechanisms involved in this process are not yet clarified. A role has been hypothesized for Human Cytomegalovirus (HCMV) and Human Herpesvirus 6 (HHV-6) infections as triggers of systemic sclerosis (SSc), a severe autoimmune disease causing progressive tissue fibrosis, since both viruses and antiviral immune responses toward them have been detected in patients. Moreover, HCMV or HHV-6A infection was reported to increase the expression of fibrosis-associated transcriptional factors and miRNAs in human dermal fibroblasts. However, it is unlikely that they have separate effects in the infected host, as both viruses are highly prevalent in the human population. Thus, our study aimed to investigate, by quantitative real-time PCR microarray, the impact of HCMV/HHV-6A coinfection on the expression of pro-fibrotic miRNAs in coinfected cells, compared to the effect of single viruses. The results showed a possible synergistic effect of the two viruses on pro-fibrotic miRNA expression, thus suggesting that HCMV and HHV-6 may enhance each other and cooperate at inducing enhanced miRNA-driven fibrosis. These data may also suggest a possible use of virus-induced miRNAs as novel diagnostic or prognostic biomarkers for SSc and its clinical treatment.
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spelling doaj.art-ea3640110cea40cbba96700e6f887e5c2023-11-16T22:15:30ZengMDPI AGMicroorganisms2076-26072023-02-0111241210.3390/microorganisms11020412Coinfection of Dermal Fibroblasts by Human Cytomegalovirus and Human Herpesvirus 6 Can Boost the Expression of Fibrosis-Associated MicroRNAsIrene Soffritti0Maria D’Accolti1Clara Maccari2Francesca Bini3Eleonora Mazziga4Maria-Cristina Arcangeletti5Elisabetta Caselli6Section of Microbiology, Department of Chemical, Pharmaceutical and Agricultural Sciences and LTTA, University of Ferrara, 44121 Ferrara, ItalySection of Microbiology, Department of Chemical, Pharmaceutical and Agricultural Sciences and LTTA, University of Ferrara, 44121 Ferrara, ItalyLaboratory of Microbiology and Virology, Department of Medicine and Surgery, University of Parma, 43126 Parma, ItalySection of Microbiology, Department of Chemical, Pharmaceutical and Agricultural Sciences and LTTA, University of Ferrara, 44121 Ferrara, ItalySection of Microbiology, Department of Chemical, Pharmaceutical and Agricultural Sciences and LTTA, University of Ferrara, 44121 Ferrara, ItalyLaboratory of Microbiology and Virology, Department of Medicine and Surgery, University of Parma, 43126 Parma, ItalySection of Microbiology, Department of Chemical, Pharmaceutical and Agricultural Sciences and LTTA, University of Ferrara, 44121 Ferrara, ItalyTissue fibrosis can affect every type of tissue or organ, often leading to organ malfunction; however, the mechanisms involved in this process are not yet clarified. A role has been hypothesized for Human Cytomegalovirus (HCMV) and Human Herpesvirus 6 (HHV-6) infections as triggers of systemic sclerosis (SSc), a severe autoimmune disease causing progressive tissue fibrosis, since both viruses and antiviral immune responses toward them have been detected in patients. Moreover, HCMV or HHV-6A infection was reported to increase the expression of fibrosis-associated transcriptional factors and miRNAs in human dermal fibroblasts. However, it is unlikely that they have separate effects in the infected host, as both viruses are highly prevalent in the human population. Thus, our study aimed to investigate, by quantitative real-time PCR microarray, the impact of HCMV/HHV-6A coinfection on the expression of pro-fibrotic miRNAs in coinfected cells, compared to the effect of single viruses. The results showed a possible synergistic effect of the two viruses on pro-fibrotic miRNA expression, thus suggesting that HCMV and HHV-6 may enhance each other and cooperate at inducing enhanced miRNA-driven fibrosis. These data may also suggest a possible use of virus-induced miRNAs as novel diagnostic or prognostic biomarkers for SSc and its clinical treatment.https://www.mdpi.com/2076-2607/11/2/412HCMVHHV-6coinfectionsystemic sclerosisfibrosismicroRNAs
spellingShingle Irene Soffritti
Maria D’Accolti
Clara Maccari
Francesca Bini
Eleonora Mazziga
Maria-Cristina Arcangeletti
Elisabetta Caselli
Coinfection of Dermal Fibroblasts by Human Cytomegalovirus and Human Herpesvirus 6 Can Boost the Expression of Fibrosis-Associated MicroRNAs
Microorganisms
HCMV
HHV-6
coinfection
systemic sclerosis
fibrosis
microRNAs
title Coinfection of Dermal Fibroblasts by Human Cytomegalovirus and Human Herpesvirus 6 Can Boost the Expression of Fibrosis-Associated MicroRNAs
title_full Coinfection of Dermal Fibroblasts by Human Cytomegalovirus and Human Herpesvirus 6 Can Boost the Expression of Fibrosis-Associated MicroRNAs
title_fullStr Coinfection of Dermal Fibroblasts by Human Cytomegalovirus and Human Herpesvirus 6 Can Boost the Expression of Fibrosis-Associated MicroRNAs
title_full_unstemmed Coinfection of Dermal Fibroblasts by Human Cytomegalovirus and Human Herpesvirus 6 Can Boost the Expression of Fibrosis-Associated MicroRNAs
title_short Coinfection of Dermal Fibroblasts by Human Cytomegalovirus and Human Herpesvirus 6 Can Boost the Expression of Fibrosis-Associated MicroRNAs
title_sort coinfection of dermal fibroblasts by human cytomegalovirus and human herpesvirus 6 can boost the expression of fibrosis associated micrornas
topic HCMV
HHV-6
coinfection
systemic sclerosis
fibrosis
microRNAs
url https://www.mdpi.com/2076-2607/11/2/412
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