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Open AccessArticle

HHV-6A Infection and Systemic Sclerosis: Clues of a Possible Association

1
Section of Microbiology and Medical Genetics, Department of Chemical and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, Italy
2
Rheumatology Unit, Medical School, University of Modena and Reggio Emilia, University-Hospital Policlinico of Modena, 41121 Modena, Italy
*
Author to whom correspondence should be addressed.
Microorganisms 2020, 8(1), 39; https://doi.org/10.3390/microorganisms8010039
Received: 6 December 2019 / Accepted: 20 December 2019 / Published: 24 December 2019
(This article belongs to the Special Issue Virus-Host Interaction: From Physiology to Pathology)
Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, excessive extracellular matrix deposition, and fibrosis of the skin and internal organs. Several infectious agents, including human herpesvirus-6 (HHV-6), have been suggested as possible triggering factors, but a direct association is still missing. We characterized 26 SSc patients for the presence of HHV-6 in tissues and blood, the anti-HHV-6 response, HLA-G plasma levels, and KIR typing. Given the prominent role of endothelial cells (EC) in SSc pathogenesis, along with HHV-6 tropism for EC, we also investigated the expression of pro-fibrosis factors in HHV-6 infected EC. Results showed the presence of HHV-6A in skin biopsies, and an increased virus load was associated with disease severity and poor natural killer (NK) response against the virus, particularly in subjects exhibiting a KIR2 phenotype. HLA-G plasma levels were significantly higher in HHV-6A/B-KIR2 positive SSc patients and in vitro HHV-6A infection-induced pro-fibrosis factors expression in EC, supporting its role in the development of the fibrosing process. Our data suggest an association between virus infection/reactivation and disease, opening the way to future studies to understand the mechanisms by which HHV-6A might contribute to the multifactorial pathogenesis of SSc. View Full-Text
Keywords: systemic sclerosis; HHV-6; immune response; HLA-G systemic sclerosis; HHV-6; immune response; HLA-G
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    Description: Suppl. Figure 1. Induction of fibrosis-associated factors by HHV-6A/B infection in human endothelial cells (HUVEC). The modulation of factors potentially associated with fibrosis development was assayed in uninfected HUVEC (CTR) or in HUVEC infected in vitro with HHV-6A, HHV-6B, or the respective UV-inactivated viruses, used as controls. Total RNA was extracted 48 hours post-infection and analyzed by a microarray quantifying simultaneously 84 factors associated with fibrosis. Results are expressed as mean values of duplicate samples in three independent experiments ± SD of fold-change compared to values detected in controls (CTR), after normalization for six housekeeping genes (β-actin, β2-microglobulin, GAPDH, HPRT1, RPLP0, and HGDC).
MDPI and ACS Style

Caselli, E.; Soffritti, I.; D’Accolti, M.; Bortolotti, D.; Rizzo, R.; Sighinolfi, G.; Giuggioli, D.; Ferri, C. HHV-6A Infection and Systemic Sclerosis: Clues of a Possible Association. Microorganisms 2020, 8, 39.

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