HHV-6 Infection and Chemokine RANTES Signaling Pathway Disturbance in Patients with Autoimmune Thyroiditis
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Date
2020
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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
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Keywords
autoimmune thyroiditis, HHV-6, RANTES, chemokine receptors