PMID- 32899126 OWN - NLM STAT- MEDLINE DCOM- 20210325 LR - 20210325 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 17 DP - 2020 Sep 3 TI - 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. LID - 10.3390/ijms21176397 [doi] LID - 6397 AB - 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. FAU - Arcangeletti, Maria-Cristina AU - Arcangeletti MC AD - Department of Medicine and Surgery, Unit of Virology, University-Hospital of Parma, University of Parma, 43126 Parma, Italy. FAU - D'Accolti, Maria AU - D'Accolti M AUID- ORCID: 0000-0003-1937-5534 AD - Department of Chemical and Pharmaceutical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, 44121 Ferrara, Italy. FAU - Maccari, Clara AU - Maccari C AD - Department of Medicine and Surgery, Unit of Virology, University-Hospital of Parma, University of Parma, 43126 Parma, Italy. FAU - Soffritti, Irene AU - Soffritti I AUID- ORCID: 0000-0002-5274-295X AD - Department of Chemical and Pharmaceutical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, 44121 Ferrara, Italy. FAU - Conto, Flora De AU - Conto F AD - Department of Medicine and Surgery, Unit of Virology, University-Hospital of Parma, University of Parma, 43126 Parma, Italy. FAU - Chezzi, Carlo AU - Chezzi C AD - Department of Medicine and Surgery, Unit of Virology, University-Hospital of Parma, University of Parma, 43126 Parma, Italy. FAU - Calderaro, Adriana AU - Calderaro A AD - Department of Medicine and Surgery, Unit of Virology, University-Hospital of Parma, University of Parma, 43126 Parma, Italy. FAU - Ferri, Clodoveo AU - Ferri C AD - 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. FAU - Caselli, Elisabetta AU - Caselli E AUID- ORCID: 0000-0001-6048-9141 AD - Department of Chemical and Pharmaceutical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, 44121 Ferrara, Italy. LA - eng GR - D92F16000490005/Ministero dell'Istruzione, dell'Universita e della Ricerca/ GR - 2015YZB22C/Ministero dell'Istruzione, dell'Universita e della Ricerca/ PT - Journal Article DEP - 20200903 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Apoptosis Regulatory Proteins) SB - IM MH - *Apoptosis MH - Apoptosis Regulatory Proteins/*metabolism MH - Cells, Cultured MH - Cytomegalovirus/isolation & purification MH - Cytomegalovirus Infections/*complications/virology MH - Dermis/metabolism/pathology/virology MH - Fibroblasts/metabolism/*pathology/virology MH - Fibrosis/metabolism/*pathology/virology MH - Herpesviridae Infections/*complications/virology MH - Herpesvirus 6, Human/isolation & purification MH - Humans MH - Scleroderma, Systemic/metabolism/*pathology/virology PMC - PMC7504027 OTO - NOTNLM OT - apoptosis OT - fibrosis OT - human cytomegalovirus OT - human herpesvirus 6 OT - systemic sclerosis COIS- The authors declare no conflict of interest. EDAT- 2020/09/10 06:00 MHDA- 2021/03/26 06:00 PMCR- 2020/09/01 CRDT- 2020/09/09 01:02 PHST- 2020/07/29 00:00 [received] PHST- 2020/08/26 00:00 [revised] PHST- 2020/08/31 00:00 [accepted] PHST- 2020/09/09 01:02 [entrez] PHST- 2020/09/10 06:00 [pubmed] PHST- 2021/03/26 06:00 [medline] PHST- 2020/09/01 00:00 [pmc-release] AID - ijms21176397 [pii] AID - ijms-21-06397 [pii] AID - 10.3390/ijms21176397 [doi] PST - epublish SO - Int J Mol Sci. 2020 Sep 3;21(17):6397. doi: 10.3390/ijms21176397.