HHV-6A in vitro infection of thyrocytes and T cells alters the expression of miRNA associated to autoimmune thyroiditis

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.

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

“…Total RNA was extracted by the miRNeasy kit following the manufacturer's instructions (Qiagen, Hilden, Germany). Elimination of contaminant DNA was assured by DNase digestions and lack of amplification in PCR reactions where retrotranscription (RT) had been omitted [44].…”

“…RNA from infected or uninfected HUVECs was extracted by the miRNeasy kit (Qiagen, Hilden, Germany) as already described [44], and analyzed by a qPCR microarray simultaneously detecting 84 factors associated with fibrosis (Qiagen, Hilden, Germany). Results represented up-or down-regulation of factors in infected versus control cells (either uninfected or infected with UV-inactivated viruses), and were expressed as fold-change compared to values detected in control cells, after normalization for six housekeeping genes (βactin, β2microglobulin, GAPDH, HPRT1, RPLP0, and HGDC).…”

Monocytes/Macrophages Act as Mediators for Human Herpesvirus-6 Infection of Thyroid Gland in Patients with Autoimmune Thyroiditis

“…Nowadays, more evidence indicates HHV-6 as a very important factor in AIT development (Rizzo et al, 2016;Caselli et al, 2017;Sultanova et al, 2017). Our previous studies showed almost 100% incidence of the HHV-6 genomic sequence in thyroid gland tissues acquired from AIT patients and insignificant presence in peripheral blood (Sultanova et al, 2016;.…”

“…HHV-6 is known to have strong immunomodulating properties, which could affect the host during a long period of time and contribute to several autoimmune disorders, in-cluding autoimmune haemolytic anaemia/neutropenia (Yagasaki et al, 2011), autoimmune acute hepatitis (Grima et al, 2008) and multiple sclerosis (Chapenko et al, 2003;Tejada-Simon et al, 2003). Recent studies pay more and more attention to the possible involvement of human herpesvirus-6 in autoimmune thyroiditis (AIT) development (Rizzo et al, 2016;Caselli et al, 2017;Sultanova et al, 2017). The contribution to several autoimmune diseases and its widespread distribution, make HHV-6 an important threat to overall health and quality of life.…”

Severe Delayed Drug Reactions

“…111–114 Recent studies have shown an association between AITD and HHV-6 infection and in vitro HHV-6 virus modulation of micro RNA expression in thyrocytes and T-cell lines. 115–118 …”