HHV-6 Infection and Chemokine RANTES Signaling Pathway Disturbance in Patients with Autoimmune Thyroiditis.

Alina Sultanova,Modra Murovska,Liba Sokolovska,Katerina Todorova,Egils Cunskis,Maksims Cistjakovs

doi:10.3390/v12060689

Abstract

The aim of this study was to investigate the role of human herpesvirus-6 (HHV-6) in autoimmune thyroiditis (AIT) development. We examined the possible involvement of HHV-6 gene expression encoding immunomodulating proteins U12 and U51 in AIT development and their role in the modulation of chemokine signaling. One hundred patients with autoimmune thyroiditis following thyroidectomy were enrolled in this study. Nested polymerase chain reaction (nPCR) was used to detect the HHV-6 sequence in DNA samples. Reverse transcription PCR (RT-PCR) with three different HHV-6 gene targets (U79/80, U51 and U12) was to detect active infection markers. HHV-6 load was identified using a commercial real-time PCR kit. Immunohistochemistry was performed to investigate the expression of the HHV-6 antigen and RANTES (Regulated upon Activation, Normal T Cell Expressed and Secreted) in thyroid gland tissue. Different commercial immunosorbent assay kits were used for the detection of RANTES, IFNγ, IL-6, and TNFα levels in the AIT patient group and controls. We detected 98% presence of the HHV-6 genomic sequence in AIT patients’ thyroid gland tissues. Markers of active HHV-6 infection (HHV-6 U79/80, U12 and/or U51 mRNA) were predominant in AIT patients’ thyroid tissue samples in comparison with the control group (56% vs. 6%). Evidence from immunofluorescence microscopy showed that HHV-6 can persist in thyrocytes and can interact with RANTES. Visual confirmation of the intense immunofluorescence signal of RANTES detected in thyroid tissues could indicate high expression of this chemokine in the thyroid gland. On the other hand, immunosorbent assays showed very low RANTES levels in AIT patients’ peripheral plasma. These results indicate that RANTES level in AIT patients could be influenced by HHV-6 activation, which in turn may aid AIT development.

Highlights

Autoimmune disease affects the thyroid more than any other organ, and the incidence of autoimmune thyroiditis (AIT) has dramatically increased over time worldwide [1]
These results indicate that RANTES level in AIT patients could be influenced by human herpesvirus-6 (HHV-6) activation, which in turn may aid AIT development
A study mapping the reservoirs of human herpesviruses detected EBV, CMV and HHV-6 in the thyroid gland tissues of eight autopsies, without detecting active infection, showing that the thyroid is potentially susceptible to herpesvirus infection

Summary

Introduction

Autoimmune disease affects the thyroid more than any other organ, and the incidence of autoimmune thyroiditis (AIT) has dramatically increased over time worldwide [1]. AIT predominantly affects women, which could be explained by differences in hormonal background [2]. Autoimmune thyroiditis (AIT) is a big challenge for researchers, as many of the etiological factors are still unknown. More and more attention has been given to the possible involvement of viruses in the development of different autoimmune diseases. AIT is no exception—some studies bring evidence of human herpesvirus-6 (HHV-6) involvement in this disease’s development. A study mapping the reservoirs of human herpesviruses detected EBV, CMV and HHV-6 in the thyroid gland tissues of eight autopsies, without detecting active infection, showing that the thyroid is potentially susceptible to herpesvirus infection.

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