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: Elisabetta Caselli, Maria Chiara Zatelli, Roberta Rizzo, Sabrina Benedetti, Debora Martorelli, Giorgio Trasforini, Enzo Cassai, Ettore C degli Uberti, Dario Di Luca, Riccardo Dolcetti
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Acceso en línea:https://doaj.org/article/ff9f57d5fee34a1a98dee635c30061b3
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spelling oai:doaj.org-article:ff9f57d5fee34a1a98dee635c30061b32021-11-18T06:06:29ZVirologic and immunologic evidence supporting an association between HHV-6 and Hashimoto's thyroiditis.1553-73661553-737410.1371/journal.ppat.1002951https://doaj.org/article/ff9f57d5fee34a1a98dee635c30061b32012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23055929/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Hashimoto'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.Elisabetta CaselliMaria Chiara ZatelliRoberta RizzoSabrina BenedettiDebora MartorelliGiorgio TrasforiniEnzo CassaiEttore C degli UbertiDario Di LucaRiccardo DolcettiPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 10, p e1002951 (2012)
institution DOAJ
collection DOAJ
language EN
topic Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
spellingShingle Immunologic diseases. Allergy
RC581-607
Biology (General)
QH301-705.5
Elisabetta Caselli
Maria Chiara Zatelli
Roberta Rizzo
Sabrina Benedetti
Debora Martorelli
Giorgio Trasforini
Enzo Cassai
Ettore C degli Uberti
Dario Di Luca
Riccardo Dolcetti
Virologic and immunologic evidence supporting an association between HHV-6 and Hashimoto's thyroiditis.
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.
format article
author Elisabetta Caselli
Maria Chiara Zatelli
Roberta Rizzo
Sabrina Benedetti
Debora Martorelli
Giorgio Trasforini
Enzo Cassai
Ettore C degli Uberti
Dario Di Luca
Riccardo Dolcetti
author_facet Elisabetta Caselli
Maria Chiara Zatelli
Roberta Rizzo
Sabrina Benedetti
Debora Martorelli
Giorgio Trasforini
Enzo Cassai
Ettore C degli Uberti
Dario Di Luca
Riccardo Dolcetti
author_sort Elisabetta Caselli
title 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_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_sort virologic and immunologic evidence supporting an association between hhv-6 and hashimoto's thyroiditis.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/ff9f57d5fee34a1a98dee635c30061b3
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