Abstract
BackgroundHuman 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.MethodsHuman 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.ResultsHHV-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.ConclusionsHHV-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.
Highlights
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 show specific anti-viral immune responses
We and others reported a high prevalence of active human herpesvirus 6A (HHV-6A) infection in thyrocytes of Hashimoto’s thyroiditis (HT) patients [2, 3], who display specific cellular and humoral anti-viral responses, increased NK killing of
Herpesvirus infection in human thyroid and T-cell lines Prior to study miRNA expression, the infection efficiency of the viruses used for the experiments was checked by quantitative PCR (qPCR) in both thyroid Nthy-ori3-1 and lymphoid Jurkat cells, showing that all virus types (HHV-6A, HHV-6B and HHV-7) were entering and replicating in both Nthy-ori3-1 and Jurkat T cells (Fig. 1), confirming what previously published [3, 5, 13]
Summary
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 show specific anti-viral immune responses. Autoimmune thyroid diseases (AITD) are very common thyroid disorders, showing increased prevalence in recent years [1]. We and others reported a high prevalence of active human herpesvirus 6A (HHV-6A) infection in thyrocytes of Hashimoto’s thyroiditis (HT) patients [2, 3], who display specific cellular and humoral anti-viral responses, increased NK killing of HHV-6 is a ubiquitous virus including two distinct viral species, HHV-6A and HHV-6B, displaying different cellular tropism and receptors usage [5,6,7,8]. HHV-6B is associated with childhood exanthema subitum, whereas HHV-6A is mostly adult-associated, and has been correlated to several chronic autoimmune inflammatory diseases, including AITD [5, 9].
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