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Virologic and Immunologic Evidence Supporting an Association between HHV-6 and Hashimoto's Thyroiditis

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 con...

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Autores principales: Caselli, Elisabetta, Zatelli, Maria Chiara, Rizzo, Roberta, Benedetti, Sabrina, Martorelli, Debora, Trasforini, Giorgio, Cassai, Enzo, degli Uberti, Ettore C., Di Luca, Dario, Dolcetti, Riccardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464215/
https://www.ncbi.nlm.nih.gov/pubmed/23055929
http://dx.doi.org/10.1371/journal.ppat.1002951
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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
author_facet Caselli, Elisabetta
Zatelli, Maria Chiara
Rizzo, Roberta
Benedetti, Sabrina
Martorelli, Debora
Trasforini, Giorgio
Cassai, Enzo
degli Uberti, Ettore C.
Di Luca, Dario
Dolcetti, Riccardo
author_sort Caselli, Elisabetta
collection PubMed
description 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.
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spelling pubmed-34642152012-10-09 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 Dolcetti, Riccardo PLoS Pathog Research Article 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. Public Library of Science 2012-10-04 /pmc/articles/PMC3464215/ /pubmed/23055929 http://dx.doi.org/10.1371/journal.ppat.1002951 Text en © 2012 Caselli et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Caselli, Elisabetta
Zatelli, Maria Chiara
Rizzo, Roberta
Benedetti, Sabrina
Martorelli, Debora
Trasforini, Giorgio
Cassai, Enzo
degli Uberti, Ettore C.
Di Luca, Dario
Dolcetti, Riccardo
Virologic and Immunologic Evidence Supporting an Association between HHV-6 and Hashimoto's Thyroiditis
title Virologic and Immunologic Evidence Supporting an Association between HHV-6 and Hashimoto's Thyroiditis
title_full Virologic and Immunologic Evidence Supporting an Association between HHV-6 and Hashimoto's Thyroiditis
title_fullStr Virologic and Immunologic Evidence Supporting an Association between HHV-6 and Hashimoto's Thyroiditis
title_full_unstemmed Virologic and Immunologic Evidence Supporting an Association between HHV-6 and Hashimoto's Thyroiditis
title_short Virologic and Immunologic Evidence Supporting an Association between HHV-6 and Hashimoto's Thyroiditis
title_sort virologic and immunologic evidence supporting an association between hhv-6 and hashimoto's thyroiditis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3464215/
https://www.ncbi.nlm.nih.gov/pubmed/23055929
http://dx.doi.org/10.1371/journal.ppat.1002951
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