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 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.
Section of Microbiology, Department of Experimental and Diagnostic Medicine, University of Ferrara, Ferrara, Italy. csb@unife.it
Elisabetta
E
Caselli
Maria Chiara
MC
Zatelli
Roberta
R
Rizzo
Sabrina
S
Benedetti
Debora
D
Martorelli
Giorgio
G
Trasforini
Enzo
E
Cassai
Ettore C
EC
degli Uberti
Dario
D
Di Luca
Riccardo
R
Dolcetti
D044963:Biopsy, Fine-Needle; D002460:Cell Line; D004279:DNA, Viral; D004847:Epithelial Cells / Q000821:virology; D050031:Hashimoto Disease / Q000209:etiology* / Q000276:immunology / Q000821:virology*; D015654:Herpesvirus 6, Human / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000821:virology; D019349:Roseolovirus Infections / Q000821:virology*; D013961:Thyroid Gland / Q000473:pathology* / Q000821:virology; D019562:Viral Load
D004279:DNA, Viral; D000949:Histocompatibility Antigens Class II