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Human herpes virus-6 involvement in development of autoimmune thyroiditis

Projekta/līguma nr.
1.1.1.2/VIAA/1/16/202,Agreement No. 9.-14.5/257
Projekta finansējums
133 806.00 EUR, including 11 37 35.00 EUR ERDF funding and 1 33 80.60 EUR State budget co-funding
Projekta vadītājs
Projekta īstenošana
01.09.2017. - 31.08.2020.

Aim

One of the objectives of the project is to develop young scientists’ skills and scientific capacity, increasing the opportunities for young scientists to start a career in scientific institutions, to improve research competencies, restore human resources and increase the number of qualified specialists

The scientific goal of this project is to study possible mechanisms of interaction between virus and host that could result in development of an autoimmune disease

Description

Human sixth herpes virus (HHV-6) is widespread. The primary infection usually occurs in early childhood. After the primary infection, HHV-6 remains in a latent state in the host for its entire lifetime. Adults have up to 90% of the IgG antibodies in blood plasma.

Since the discovery of the virus, HHV-6 has been associated with a wide range of chronic diseases and clinical conditions due to its ubiquitous nature. Its distribution into two separate species (HHV-6A and HHV-6B) only increased issues related to involvement of this viral infection in the aetiopathogenesis of various diseases

Recent studies suggest the potential role of HHV-6 in the development of several autoimmune diseases, including autoimmune acute hepatitis (Grima et al., 2008) and autoimmune haemolytic anaemia/neutropenia (Yagasaki et al., 2011). The study performed in 2012 linked HHV-6A to Hashimoto's thyroiditis (Caselli et al., 2012).

A study carried out in A. Kirhenšteins Institute of Microbiology and Virology showed almost 100% of HHV-6B genotype sequences in thyroid tissues obtained from patients suffering from autoimmune tyreoiditis.

The most common autoimmune thyroid diseases are Hashimoto's thyroiditis and Graves disease. In some populations, the incidence of Hashimoto's thyroiditis is approximately 0.3 to 5 per 1,000 persons. It affects women more than men, and can occur at any age, including early childhood, but is most commonly observed in the age group of 30-60 years. The exact statistics of autoimmune thyroiditis incidence in the Latvian population are not yet known.

HHV-6 contains two genes (U12 and U51 encoding G protein-coupled receptor (GCR) predicted homologues on the cell surface). Proteins encoded by U12 and U51 genes can be expressed on the surface of epithelial cell and some peripheral blood mononuclear cell populations, which makes them the potential cause of autoimmune process and make auto-reactive T and B lymphocytes target the host’s GCR. HHV-6 specific GCR can also interact in vitro with the cytokine signaling pathway, causing lower regulation of RANTES. Both these facts make U12 and U51 proteins perfect for studying HHV-6 role in the development of autoimmune thyroiditis.

Specific antigens are required to study the role of HHV-6 U12 and U51 proteins in the development of autoimmune thyroiditis, although these proteins are hard to obtain for the study in the form of recombinant proteins due to their properties. This issue could be solved by using various synthetic peptides that could be used as antigens in immunological studies, which is one of the goals of this study.

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