title: HHV-6A in vitro infection of thyrocytes and T cells alters the expression of miRNA associated to autoimmune thyroiditis.
abstract: Human herpesviruses have been hypothesized as environmental triggers in the development of autoimmune thyroid diseases (AITD), and in particular active human herpesvirus 6A (HHV-6A) infection was detected in thyrocytes of Hashimoto's thyroiditis (HT) patients, who also show specific anti-viral immune responses. On the other hand, AITD patients display modulation of specific miRNAs in thyroid tissue and blood. We wanted to ascertain whether HHV-6A infection might be correlated to the miRNA dysregulation observed in AITD.
  
  
  
  Human thyroid and T-cell lines were infected in vitro with HHV-6A,-6B or -7, and analysed for miRNAs expression, either by microarray or by specific RT-PCR assays detecting miRNAs associated with AITD in vivo.
  
  
  
  HHV-6A infection, but not -6B or -7 infections, induced a decrease in miR-155_2 expression and an increase in miR-1238 expression in thyrocytes, as well as an increase in the expression levels of several autoimmunity-associated miRNAs in T lymphocytes, including miR-16_1, miR34a, miR-130a, miR-143_1, miR-202, miR-301b, miR-302c, miR-449b, miR-451_1, and miR-1238_2.
  
  
  
  HHV-6A infection modulates miRNAs expression in the cell types involved in the development of AITD. Notably, our in vitro findings correlate with what observed in AITD patients, further supporting the association between HHV-6A infection and AITD development. Moreover, these effects are 6A-specific, emphasizing the differences between the two HHV-6 virus species, and suggesting diverse virus mechanisms of action and therapeutic approaches.
authors.affiliation: Department of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, via L. Borsari 46, 44121, Ferrara, Italy. elisabetta.caselli@unife.it.
authors.forename: Elisabetta
authors.identifier: 0000-0001-6048-9141
authors.initials: E
authors.lastname: Caselli
authors.affiliation: Department of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, via L. Borsari 46, 44121, Ferrara, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: D'Accolti
authors.affiliation: Department of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, via L. Borsari 46, 44121, Ferrara, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Soffritti
authors.affiliation: Department of Medical Sciences, Section of Endocrinology and Internal Medicine, University of Ferrara, via A. Moro 8, 44124, Ferrara, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Zatelli
authors.affiliation: Endocrinology Unit, Azienda Ospedaliero-Universitaria di Ferrara, via A. Moro 8, 44124, Ferrara, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Rossi
authors.affiliation: Department of Medical Sciences, Section of Endocrinology and Internal Medicine, University of Ferrara, via A. Moro 8, 44124, Ferrara, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Degli Uberti
authors.affiliation: Department of Medical Sciences, Section of Microbiology and Medical Genetics, University of Ferrara, via L. Borsari 46, 44121, Ferrara, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Di Luca
mesh_terms: D020869:Gene Expression Profiling; D015654:Herpesvirus 6, Human / Q000254:growth & development*; D016199:Herpesvirus 7, Human / Q000254:growth & development; D006801:Humans; D035683:MicroRNAs / Q000032:analysis*; D046228:Microarray Analysis; D060888:Real-Time Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000821:virology*; D000072637:Thyroid Epithelial Cells / Q000821:virology*; D013967:Thyroiditis, Autoimmune / Q000473:pathology*
chemical_list: D035683:MicroRNAs
keywords: Autoimmune thyroiditis; HHV-6; miRNA