{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:20:22Z","timestamp":1790835622982,"version":"4.1.0"},"reference-count":103,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T00:00:00Z","timestamp":1599091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["D92F16000490005"],"award-info":[{"award-number":["D92F16000490005"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["2015YZB22C"],"award-info":[{"award-number":["2015YZB22C"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Systemic sclerosis (SSc) is a severe autoimmune disorder characterized by vasculopathy and multi-organ fibrosis; its etiology and pathogenesis are still largely unknown. Herpesvirus infections, particularly by human cytomegalovirus (HCMV) and human herpesvirus 6 (HHV-6), have been suggested among triggers of the disease based on virological and immunological observations. However, the direct impact of HCMV and\/or HHV-6 infection on cell fibrosis and apoptosis at the cell microenvironment level has not yet been clarified. Thus, this study aimed to investigate the effects of HCMV and HHV-6 infection on the induction of pro-fibrosis or pro-apoptosis conditions in primary human dermal fibroblasts, one of the relevant SSc target cells. The analysis, performed by microarray in in vitro HCMV- or HHV-6-infected vs. uninfected cells, using specific panels for the detection of the main cellular factors associated with fibrosis or apoptosis, showed that both viruses significantly modified the expression of at least 30 pro-fibrotic and 20 pro-apoptotic factors. Notably, several recognized pro-fibrotic factors were highly induced, and most of them were reported to be involved in vivo in the multifactorial and multistep pathogenic process of SSc, thus suggesting a potential role of both HCMV and HHV-6.<\/jats:p>","DOI":"10.3390\/ijms21176397","type":"journal-article","created":{"date-parts":[[2020,9,3]],"date-time":"2020-09-03T08:40:26Z","timestamp":1599122426000},"page":"6397","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Impact of Human Cytomegalovirus and Human Herpesvirus 6 Infection on the Expression of Factors Associated with Cell Fibrosis and Apoptosis: Clues for Implication in Systemic Sclerosis Development"],"prefix":"10.3390","volume":"21","author":[{"given":"Maria-Cristina","family":"Arcangeletti","sequence":"first","affiliation":[{"name":"Department of Medicine and Surgery, Unit of Virology, University-Hospital of Parma, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1937-5534","authenticated-orcid":false,"given":"Maria","family":"D\u2019Accolti","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Maccari","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Unit of Virology, University-Hospital of Parma, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5274-295X","authenticated-orcid":false,"given":"Irene","family":"Soffritti","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flora De","family":"Conto","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Unit of Virology, University-Hospital of Parma, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Chezzi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Unit of Virology, University-Hospital of Parma, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Calderaro","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Unit of Virology, University-Hospital of Parma, University of Parma, 43126 Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clodoveo","family":"Ferri","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences for Children and Adults, Rheumatology Unit, University-Hospital Policlinico of Modena, University of Modena and Reggio Emilia, 41121 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6048-9141","authenticated-orcid":false,"given":"Elisabetta","family":"Caselli","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1097\/00005792-200203000-00004","article-title":"Systemic sclerosis: Demographic, clinical, and serologic features and survival in 1,012 Italian patients","volume":"81","author":"Ferri","year":"2002","journal-title":"Medicine"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/S0889-857X(03)00023-1","article-title":"Natural history of systemic sclerosis and the assessment of disease activity, severity, functional status, and psychologic well-being","volume":"29","author":"Medsger","year":"2003","journal-title":"Rheum. 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