PMID- 23055929
OWN - NLM
STAT- MEDLINE
DCOM- 20130404
LR  - 20211021
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 8
IP  - 10
DP  - 2012
TI  - Virologic and immunologic evidence supporting an association between HHV-6 and 
      Hashimoto's thyroiditis.
PG  - e1002951
LID - 10.1371/journal.ppat.1002951 [doi]
LID - e1002951
AB  - 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.
FAU - Caselli, Elisabetta
AU  - Caselli E
AD  - Section of Microbiology, Department of Experimental and Diagnostic Medicine, 
      University of Ferrara, Ferrara, Italy. csb@unife.it
FAU - Zatelli, Maria Chiara
AU  - Zatelli MC
FAU - Rizzo, Roberta
AU  - Rizzo R
FAU - Benedetti, Sabrina
AU  - Benedetti S
FAU - Martorelli, Debora
AU  - Martorelli D
FAU - Trasforini, Giorgio
AU  - Trasforini G
FAU - Cassai, Enzo
AU  - Cassai E
FAU - degli Uberti, Ettore C
AU  - degli Uberti EC
FAU - Di Luca, Dario
AU  - Di Luca D
FAU - Dolcetti, Riccardo
AU  - Dolcetti R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121004
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (DNA, Viral)
RN  - 0 (Histocompatibility Antigens Class II)
SB  - IM
MH  - Biopsy, Fine-Needle
MH  - Cell Line
MH  - DNA, Viral
MH  - Epithelial Cells/virology
MH  - Hashimoto Disease/*etiology/immunology/*virology
MH  - Herpesvirus 6, Human/genetics/immunology/isolation & purification/*pathogenicity
MH  - Histocompatibility Antigens Class II/biosynthesis
MH  - Humans
MH  - Killer Cells, Natural/immunology
MH  - Leukocytes, Mononuclear/virology
MH  - Roseolovirus Infections/*virology
MH  - Thyroid Gland/*pathology/virology
MH  - Viral Load
PMC - PMC3464215
COIS- The authors have declared that no competing interests exist.
EDAT- 2012/10/12 06:00
MHDA- 2013/04/05 06:00
PMCR- 2012/10/04
CRDT- 2012/10/12 06:00
PHST- 2012/05/16 00:00 [received]
PHST- 2012/08/22 00:00 [accepted]
PHST- 2012/10/12 06:00 [entrez]
PHST- 2012/10/12 06:00 [pubmed]
PHST- 2013/04/05 06:00 [medline]
PHST- 2012/10/04 00:00 [pmc-release]
AID - PPATHOGENS-D-12-01343 [pii]
AID - 10.1371/journal.ppat.1002951 [doi]
PST - ppublish
SO  - PLoS Pathog. 2012;8(10):e1002951. doi: 10.1371/journal.ppat.1002951. Epub 2012 
      Oct 4.