Possible Involvement of Human Herpesvirus-6 U83 Gene Expression in Autoimmune Thyroiditis Development

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Viral infections have been frequently cited as important environmental factors implicated in autoimmune thyroiditis (AIT) development, although no specific virus has yet been conclusively associated with the disease. Some evidence implicates human herpesvirus-6 (HHV-6) in this disease. The aim of this study was to investigate the role of the HHV-6 U83 gene expression in autoimmune thyroiditis development. Fifty-one patients with AIT following thyroidectomy and a control group of 30 autopsied subjects without thyroid pathologies for comparing virology results and 30 healthy blood donors for comparing serology results were enrolled in this study. HHV-6 U83 gene expression was determined using nested PCR with complementary DNA as the template acquired from thyroid gland extracted RNA. Plasma samples of AIT patients and blood donors were tested for IL-2, IL-4, IL-10, sTNF-RII and IL-1beta levels by ELISA. Virology results were compared with pro- and anti-inflammatory cytokine levels to determine possible interaction of HHV-6 with host immune response. HHV-6 U83 gene expression was found only in 24% (12/49) of AIT patient thyroid gland tissue samples and in none of the control group individuals, showing possible involvement of this gene in AIT development. However, no interaction between HHV-6 and changes in cytokine levels was found.

Agut, H., Bonnafous, P., Gautheret-Dejeana, A. (2015). Laboratory and clinical aspects of human herpesvirus 6 infections. Clin. Microbiol. Rev., 28 (2), 313–335.

Aster, J., Kumar, V., Abbas, A. K., Fausto N. (2009). Robbins Cotran Pathologic Basis of Disease. 8th edn. Saunders, Philadelphia. 1464 pp. (at p. 54).

Broccolo, F., Fusetti, L., Ceccherini-Nelli, L. (2013). Possible role of human herpesvirus 6 as a trigger of autoimmune disease. Sci. World J., 2013, 867389.

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.

Chen, T., Hudnall, S. D. (2006). Anatomical mapping of human herpesvirus reservoirs of infection. Mod. Pathol., 19, 726–737.

Costa, F. A., Soki, M. N., Andrade, P. D., Bonon, S. H., Thomasini, R. L., Sampaio, A. M., Ramos, Mde. C., Rossi, C. L., Cavalcanti, T. C., Boin, Ide. F., Leonard, M., Leonard, L. S., Stucchi, R. B., Costa, S. C. (2011). Simultaneous monitoring of CMV and human herpesvirus 6 infections and diseases in liver transplant patients: One-year follow-up. Clinics (Sao Paulo), 66 (6), 949–953.

Grima, P., Chiavaroli, R., Calabrese, P., Tundo, P. (2008). Severe hepatitis with autoimmune features following a HHV-6: A case report. Cases J., 1 (1), 110.

Hershey, G. K., Friedrich, M. F., Esswein, L. A., Thomas, M. L., Chatila, T. A. (1997). The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor. New Engl. J. Med., 337 (24), 1720–1725.

Isegawa, Y., Ping, Z., Nakano, K., Sugimoto, N., Yamanishi, K. (1998). Human herpesvirus 6 open reading frame U12 encodes a functional b-chemokine receptor. J. Virol., 72, 6104–6112.

Lerner, A., Jeremias, P., Matthias, T. (2015). The world incidence and prevalence of autoimmune diseases is increasing. Int. J. Celiac Dis., 3 (4), 151–155.

Menotti, L., Mirandola, P., Locati, M., Campadelli-Fiume, G. (1999). Trafficking to the plasma membrane of the seven-transmembrane protein encoded by human herpesvirus 6 U51 gene involves a cellspecific function present in T lymphocytes. J. Virol., 73, 325–333.

Milne, R. S., Mattick, C., Nicholson, L., Devaraj, P., Alcami, A., Gompels, U. A. (2000). RANTES binding and down-regulation by a novel human herpesvirus-6 b-chemokine receptor. J. Immunol., 164, 2396–2404.

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.

Sjahril, R., Isegawa, Y., Tanaka, T., Nakano, K. Yoshikawa, T., Asano, Y., Ohshima, A., Yamanishi, K., Sugimoto, N. (2009). Relationship between U83 gene variation in human herpesvirus 6 and secretion of the U83 gene product. Arch. Virol., 154 (2), 273–283.

Sultanova, A., Cistjakovs, M., Gravelsina, S., Chapenko, S., Roga, S., Cunskis, E., Nora-Krukle, Z., Groma, V., Ventina, I., Murovska, M. (2017). Association of active human herpesvirus-6 (HHV-6) infection with autoimmune thyroid gland diseases. Clin. Microbiol. Infect., 23 (1), 50.e1–50.e5.

Tejada-Simon, M. V., Zang, YC, 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.

Vandamme, A. M., Fransen, K., Debaisieux, L., Marissens, D., Sprecher, S., Vaira, D., Vandenbroucke, A. T., Verhofstede, C. (1995). Standardisation of primers and an algorithm for HIV-1 diagnostic PCR evaluated in patients harbouring strains of diverse geographical origin. The Belgian AIDS Reference Laboratories. J. Virol. Methods., 51 (2–3), 305–316.

Wang, F., Chi, J., Peng, G., Zhou, F. Wang, J., Li, L., Feng, D., Xie, F., Gu, B., Qin, J., Chen, Y., Yao, K. (2014). Development of virus-specific CD4+ and CD8+ regulatory T cells induced by human herpesvirus 6 infection. J. Virol., 88 (2), 1011–1024.

Wells, T. N., Schwartz, T. W. (1997). Plagiarism of the host immune system: Lessons about chemokine immunology from viruses. Curr. Opin. Biotechnol., 8, 741–748.

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.

Zou, P., Isegawa, Y., Nakano, K., Haque, M., Horiguchi, Y., Yamanishi, K. (1999). Human herpesvirus 6 open reading frame U83 encodes a functional chemokine. J. Virol., 73, 5926–5933.

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CiteScore 2018: 0.3

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