Microorganisms (Dec 2019)

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

  • Elisabetta Caselli,
  • Irene Soffritti,
  • Maria D’Accolti,
  • Daria Bortolotti,
  • Roberta Rizzo,
  • Gianluca Sighinolfi,
  • Dilia Giuggioli,
  • Clodoveo Ferri

DOI
https://doi.org/10.3390/microorganisms8010039
Journal volume & issue
Vol. 8, no. 1
p. 39

Abstract

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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.

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