Virologic and immunologic evidence supporting an association between HHV-6 and Hashimoto's thyroiditis

Caselli, Elisabetta, Zatelli, Maria Chiara, Rizzo, Roberta, Benedetti, Sabrina, Martorelli, Debora, Trasforini, Giorgio, Cassai, Enzo, degli Uberti, Ettore C., Di Luca, Dario and Dolcetti, Riccardo (2012) Virologic and immunologic evidence supporting an association between HHV-6 and Hashimoto's thyroiditis. PLoS Pathogens, 8 10: . doi:10.1371/journal.ppat.1002951


Author Caselli, Elisabetta
Zatelli, Maria Chiara
Rizzo, Roberta
Benedetti, Sabrina
Martorelli, Debora
Trasforini, Giorgio
Cassai, Enzo
degli Uberti, Ettore C.
Di Luca, Dario
Dolcetti, Riccardo
Title Virologic and immunologic evidence supporting an association between HHV-6 and Hashimoto's thyroiditis
Journal name PLoS Pathogens   Check publisher's open access policy
ISSN 1553-7366
1553-7374
Publication date 2012-10-04
Year available 2012
Sub-type Article (original research)
DOI 10.1371/journal.ppat.1002951
Open Access Status DOI
Volume 8
Issue 10
Total pages 10
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Language eng
Formatted abstract
Hashimoto's thyroiditis (HT) is the most common of all thyroid diseases and is characterized by abundant lymphocyte infiltrate and thyroid impairment, caused by various cell- and antibody-mediated immune processes. Viral infections have been suggested as possible environmental triggers, but conclusive data are not available. We analyzed the presence and transcriptional state of human herpesvirus 6 (HHV-6) in thyroid fine needle aspirates (FNA) and peripheral blood mononuclear cells (PBMCs) from 34 HT patients and 28 controls, showing that HHV-6 DNA prevalence (82% vs. 10%, p≤0.001) and viral load were significantly increased in FNA from HT patients, and thyrocytes from HT FNA displayed a 100-fold higher HHV-6 DNA load compared to infiltrating lymphocytes. In addition, while HHV-6 was strictly latent in positive samples from controls, a low grade acute infection was detected in HT samples. HHV-6 variant characterization was carried out in 10 HT FNA samples, determining that all specimens harbored HHV-6 Variant A. The tropism of HHV-6 for thyroid cells was verified by infection of Nthy-ori3-1, a thyroid follicular epithelial cell line, showing that thyrocytes are permissive to HHV-6 replication, which induces de novo expression of HLA class II antigens. Furthermore, HHV-6-infected Nthy-ori3-1 cells become targets for NK-mediated killing, NK cells from HT patients show a significantly more efficient killing of HHV-6 infected thyroid cells than healthy controls, and HT patients have increased T-cell responses to HHV-6 U94 protein, associated to viral latency. These observations suggest a potential role for HHV-6 (possibly variant A) in the development or triggering of HT.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
 
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