ArticleThe Journal of investigative dermatology2014
Epstein-Barr virus infection induces aberrant TLR activation pathway and fibroblast-myofibroblast conversion in scleroderma.
Article in The Journal of investigative dermatology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 100 citations in OpenAlex.
- Cellular crosstalk of fibroblast-myofibroblast transition in intestinal homeostasis and disease.Biomarker research · 2026Review
- Unravelling the Viral Hypothesis of Schizophrenia: A Comprehensive Review of Mechanisms and Evidence.International journal of molecular sciences · 2025Review
- Mendelian randomization unveils genetic causal relationships between viral infections and systemic sclerosis.Scientific reports · 2025Article
- Extracellular Vesicles as a Potential Biomarker of Pulmonary Arterial Hypertension in Systemic Sclerosis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Antigen-presenting fibroblasts: emerging players in immune modulation and therapeutic targets.Theranostics · 2025Review
- Strong association of TLR2 and TLR3 polymorphisms with keratoacanthoma and common warts: a case-control study.Croatian medical journal · 2024Article
- Epstein-Barr Virus Promotes Inflammatory Cytokine Production in Human Gingival Fibroblasts.International dental journal · 2024Article
- Review
- Clinical characteristics and disease course before and after SARS-CoV-2 infection in a large cohort of systemic sclerosis patients.Turkish journal of medical sciences · 2024Article
- Current Concepts on the Pathogenesis of Systemic Sclerosis.Clinical reviews in allergy & immunology · 2023Review
- Epstein-Barr Virus Regulates Endothelin-1 Expression through the ERK/FOXO1 Pathway in EBV-Associated Gastric Cancer.Microbiology spectrum · 2023Article
- Therapeutic potential of mesenchymal stem cells for refractory inflammatory and immune skin diseases.Human vaccines & immunotherapeutics · 2022Article
- Serum microRNAs in Systemic Sclerosis, Associations with Digital Vasculopathy and Lung Involvement.International journal of molecular sciences · 2022Article
- The Role of Exposomes in the Pathophysiology of Autoimmune Diseases II: Pathogens.Pathophysiology : the official journal of the International Society for Pathophysiology · 2022Review
- The Immunogenetics of Systemic Sclerosis.Advances in experimental medicine and biology · 2022Article
- Upcoming treatments for morphea.Immunity, inflammation and disease · 2021Review
- Anti-viral and pro-inflammatory functions of Toll-like receptors during gamma-herpesvirus infections.Virology journal · 2021Review
- Activation of CpG-ODN-Induced TLR9 Signaling Inhibited by Interleukin-37 in U937 Human Macrophages.Yonsei medical journal · 2021Article
- Similarities between COVID-19 and systemic sclerosis early vasculopathy: A "viral" challenge for future research in scleroderma.Autoimmunity reviews · 2021Review
- Nutraceutical Curcumin with Promising Protection against Herpesvirus Infections and Their Associated Inflammation: Mechanisms and Pathways.Microorganisms · 2021Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Scleroderma (SSc) is a complex and heterogeneous connective tissue disease mainly characterized by autoimmunity, vascular damage, and fibrosis that mostly involve the skin and lungs. Epstein-Barr virus (EBV) is a lymphotropic γ-herpesvirus that has co-evolved with human species, infecting >95% of the adult population worldwide, and has been a leading candidate in triggering several autoimmune diseases. Here we show that EBV establishes infection in the majority of fibroblasts and endothelial cells in the skin of SSc patients, characterized by the expression of the EBV noncoding small RNAs (EBERs) and the increased expression of immediate-early lytic and latency mRNAs and proteins. We report that EBV is able to persistently infect human SSc fibroblasts in vitro, inducing an aberrant innate immune response in infected cells. EBV-Toll-like receptor (TLR) aberrant activation induces the expression of selected IFN-regulatory factors (IRFs), IFN-stimulated genes (ISGs), transforming growth factor-β1 (TGFβ1), and several markers of fibroblast activation, such as smooth muscle actin and Endothelin-1, and all of these genes play a key role in determining the profibrotic phenotype in SSc fibroblasts. These findings imply that EBV infection occurring in mesenchymal, endothelial, and immune cells of SSc patients may underlie the main pathological features of SSc including autoimmunity, vasculopathy, and fibrosis, and provide a unified disease mechanism represented by EBV reactivation.
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Registered trials
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