Modulation of microRNome by Human Cytomegalovirus and Human Herpesvirus 6 Infection in Human Dermal Fibroblasts: Possible Significance in the Induction of Fibrosis in Systemic Sclerosis
Human cytomegalovirus (HCMV) and Human herpesvirus 6 (HHV-6) have been reportedly
suggested as triggers of the onset and/or progression of systemic sclerosis (SSc), a severe
autoimmune disorder characterized by multi-organ fibrosis. The etiology and pathogenesis of SSc
are still largely unknown but virological and immunological observations support a role for these
beta-herpesviruses, and we recently observed a direct impact of HCMV and HHV-6 infection on
the expression of cell factors associated with fibrosis at the cell level. Since miRNA expression has
been found profoundly deregulated at the tissue level, here we aimed to investigate the impact on
cell microRNome (miRNome) of HCMV and HHV-6 infection in in vitro infected primary human
dermal fibroblasts, which represent one of the main SSc target cells. The analysis, performed by
Taqman arrays detecting and quantifying 754 microRNAs (miRNAs), showed that both herpesviruses
significantly modulated miRNA expression in infected cells, with evident early and late effects and
deep modulation (>10 fold) of >40 miRNAs at each time post infection, including those previously
recognized for their key function in fibrosis. The correlation between these in vitro results with
in vivo observations is strongly suggestive of a role of HCMV and/or HHV-6 in the multistep pathogenesis
of fibrosis in SSc and in the induction of fibrosis-signaling pathways finally leading to tissue
fibrosis. The identification of specific miRNAs may open the way to their use as biomarkers for SSc
diagnosis, assessment of disease progression and possible antifibrotic therapies
