Investigators at the University of Ferrara have uncovered intriguing alterations in intracellular regulation of HHV-6A-infected thyrocytes and T cells. Specifically, they found that HHV-6A, but not HHV-6B nor HHV-7, altered expression of several microRNAs (miRNAs), in a pattern that is considered a marker for patients with autoimmune thyroid disease (AITD).
MiRNAs regulate cellular activity by binding and silencing mRNA, thereby working as post-transcriptional regulators. They are integral to normal functioning of the cell, so miRNA dysregulation can cause serious diseases, including cancer and atherosclerosis. Notably, they also appear to be heavily involved in immunity (Baltimore 2008).
To characterize miRNA expression, the investigators extracted and retro-transcribed cellular miRNA from HHV-6A, HHV-6B, and HHV-7 infected cells at various timepoints post-infection. While HHV-6A infection of thyrocytes did not promote changes in the expression of >80 miRNAs involved in inflammation and autoimmunity, infection of T cells induced strong upregulation of several of these miRNAs. Next, the team analyzed expression of miRNAs associated with AITD and discovered that at all times post-infection, HHV-6A+ thyroid cells expressed significantly less miR-155_2 and significantly more miR-1238_2. They also detected significantly more miR-16_1, miR-143_1, miR-451_1, and miR-1238_2 in T cells. The only other alteration was a slight increase in miR-155_2 (AITD-associated miRNA) levels in HHV-7 infected T cells.
An association between HHV-6A and AITD has been documented (Thomas 2008, Descamps 2013, Sultanova 2017, Ozaki 2005, Caselli 2012, Rizzo 2016), but the mechanisms by which HHV-6A is able to induce autoimmunity in the thyroid have been relatively unclear.
While future studies will elucidate the precise functions of the miRNAs affected by HHV-6A infection, the results from this study provide strong evidence for the relationship between HHV-6A and AITD. In addition, the results could have implications for understanding the pathogenesis of other conditions with which HHV-6A has been associated, including MS, female infertility, and certain cancers.
The study was led by Elisabetta Caselli, PhD and Dario DiLuca, PhD.
Read the full paper here: Caselli 2017