Human herpesvirus-6 (HHV-6) is a ubiquitous betaherpesvirus with immunomodulating properties that have been suggested to play an important role in the development of several autoimmune disorders. Although the primary targets for HHV-6 replication, both in vitro and in vivo, are CD4+ and CD8+ T lymphocytes, some studies have reported the presence of HHV-6 sequences in different solid organs, including in the thyroid gland, showing possible involvement of this herpesvirus in development of autoimmune thyroid disease. The aim of this study was to determine loads of HHV-6 in thyroid gland tissue in comparison to those in peripheral blood of patients with autoimmune thyroiditis. Seven patients [women mean age 45 (28-65)] with histologically confirmed autoimmune thyroiditis were enrolled in this study. Fluorescence-activated cell sorting was used to distinguish and sort lymphocyte populations from peripheral blood mononuclear cells of patients. HHV-6 load was determined by real-time PCR for peripheral blood and thyroid gland tissue samples. Additionally, all results from molecular analyses were compared with histological results obtained by light microscopy. Viral load was detected only in one (46 viral copies/ 1×106cells) blood sample; others were under the detection limit of the used kit. However, in all HHV-6 positive tissue samples viral load was detected in the range of 132-1620 viral copies/106 cells. Substantial HHV-6 load in lymphocyte subpopulations was detected in two of seven patients. HHV-6 load was detected in NK and CD95+ cells of two patients. The obtained results show that thyroid gland cells (tyrocytes) act as target cells for HHV-6.
If the inline PDF is not rendering correctly, you can download the PDF file here.
Ablashi D. Agut H. Alvarez-Lafuente R. Clark D. A. Dewhurst S. DiLuca D. Flamand L. Frenkel N. Gallo R. Gompels U. A. Höllsberg P. Jacobson S. Luppi M. Lusso P. Malnati M. Medveczky P. Mori Y. Pellett P. E. Pritchett J. C. Yamanishi K. Yoshikawa T. (2014). Classification of HHV-6A and HHV-6B as distinct viruses. Arch. Virol. 159 (5) 863-870.
Alvarez-Lafuente R. Aguilera B. Suárez-Mier M. A. Morentin B. Vallejo G. Gómez J. Fernández-Rodríguez A. (2008). Detection of human herpesvirus-6 Epstein-Barr virus and cytomegalovirus in formalin- fixed tissues from sudden infant death: A study with quantitative real-time PCR. Forensic Sci. Int. 178 (2-3) 106-111.
Caselli E. Zatelli M. C. Rizzo R. Benedetti S. Martorelli D. Trasforini G. Cassai E. degli Uberti E. C. Di Luca D. Dolcetti R. (2012). Virologic and immunologic evidence supporting an association between HHV-6 and Hashimoto’s thyroiditis. PLoS Pathog. 8 (10) e1002951.
Chapenko S Millers A Nora Z Logina I Kukaine R Murovska M. (2003). Correlation between HHV-6 reactivation and multiple sclerosis disease activity. J. Med. Virol. 69 (1) 111-117.
Chen T. Hudnall S. D. (2006). Anatomical mapping of human herpesvirus reservoirs of infection. Mod. Pathol. 19 (5) 726-737.
Dagna L. Pritchett J. C. Lusso P. (2013). Immunomodulation and immunosuppression by human herpesvirus 6A and 6B. Future Virol. 8 (3) 273-287.
Grima P. Chiavaroli R. Calabrese P. Tundo P. Grima P. (2008). Severe hepatitis with autoimmune features following a HHV-6: A case report. Cases J. 1 (1) 110.
Hall C. B. Caserta M. T. Schnabel K. C. Long C. Epstein L. G. Insel R. A. Dewhurst S. (1998). Persistence of human herpesvirus 6 according to site and variant: Possible greater neurotropism of variant A. Clin. Infect. Dis. 26 (1) 132-137.
Lusso P. (2006). HHV-6 and the immune system: Mechanisms of immunomodulation and viral escape. J. Clin. Virol. 37 (Suppl 1) S4-10.
McHenry C. R. Phitayakorn R. (2011). Follicular adenoma and carcinoma of the thyroid gland. Oncologist 16 (5) 585-593.
Nikiforova M. N. Lynch R. A. Biddinger P. W. Alexander E. K. Dorn G. W. 2nd Tallini G. Kroll T. G. Nikiforov Y. E. (2003). RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: Evidence for distinct molecular pathways in thyroid follicular carcinoma. J. Clin. Endocrinol. Metab. 88 (5) 2318-2326.
Secchiero P. Carrigan D. R. Asano Y. Benedetti L. Crowley R. W. Komaroff A. L. Gallo R. C. Lusso P. (1995). Detection of human herpesvirus 6 in plasma of children with primary infection and immunosuppressed patients by polymerase chain reaction. J. Infect. Dis. 171 (2) 273-280.
Nora-Krukle Z. Chapenko S. Logina I Millers A Platkajis A Murovska M. (2011). Human herpesvirus 6 and 7 reactivation and disease activity in multiple sclerosis. Medicina (Kaunas) 47 (10) 527-531.
Santoro F. Kennedy P. E. Locatelli G. Malnati M. S. Berger E. A. Lusso P. (1999). CD46 Is a cellular receptor for human herpesvirus 6. Cell 99 817-827.
Tejada-Simon M. V. Zang Y. C. Hong J. Rivera V. M. Zhang J. Z. (2003). Cross-reactivity with myelin basic protein and human herpesvirus-6 in multiple sclerosis. Ann. Neurol. 53 (2) 189-197.
Thomas D. Liakos V. Michou V. Kapranos N. Kaltsas G. Tsilivakos V. Tsatsoulis A. (2008). Detection of herpes virus DNA in post-operative thyroid tissue specimens of patients with autoimmune thyroid disease. Exp. Clin. Endocrinol. Diabetes 116 (1) 35-39.
Yagasaki H. Kato M. Shimizu N. Shichino H. Chin M. Mugishima H. (2011). Autoimmune hemolytic anemia and autoimmune neutropenia in a child with erythroblastopenia of childhood (TEC) caused by human herpesvirus-6 (HHV-6). Ann. Hematol. 90 (7) 851-852.