Abstract
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.
Highlights
Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by immunological abnormalities, vasculopathy, and excessive extracellular matrix deposition, which leads to vascular involvement, apoptosis, and fibrosis of the skin and internal organs [1,2,3,4,5,6,7]. SSc patients can present extremely heterogeneous clinical pictures, two well-recognized subgroups have been identified according to the extent of skin involvement: patients with widespread skin involvement and patients with limited skin involvement [8]
The results show that human cytomegalovirus (HCMV) DNA copies/mL gradually increased from day 4 to day 14 p.i. in parallel with the characteristic cytopathic effect (Table 1)
The results showed, as expected, an initial increase of HHV-6A DNA followed by a gradual decrease till the end of the experiment (14 days p.i.), suggesting the initial establishment of an active replication rapidly followed by a latent infection (Table 2)
Summary
Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by immunological abnormalities, vasculopathy, and excessive extracellular matrix deposition, which leads to vascular involvement, apoptosis, and fibrosis of the skin and internal organs [1,2,3,4,5,6,7]. SSc patients can present extremely heterogeneous clinical pictures, two well-recognized subgroups have been identified according to the extent of skin involvement: patients with widespread skin involvement (diffuse cutaneous subset; dcSSc) and patients with limited skin involvement (limited cutaneous subset; lcSSc) [8]. Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by immunological abnormalities, vasculopathy, and excessive extracellular matrix deposition, which leads to vascular involvement, apoptosis, and fibrosis of the skin and internal organs [1,2,3,4,5,6,7]. Persistent/latent viral infections, such as human cytomegalovirus (HCMV) and human herpesvirus 6 (HHV-6) infections, have been evoked as possibly involved in the pathogenesis of SSc [13,15,16]. Both viruses belong to the Betaherpesvirinae subfamily, are genetically related, and have a worldwide distribution, sustaining primary infection usually early in life and establishing a latent infection lifelong in the host
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
