University of Jyväskylä

Dissertation: 16.6.2017: The autoimmune diseases caused by parvovirus can be prevented in the future

Start date: Jun 16, 2017 12:00 PM

End date: Jun 16, 2017 03:00 PM

Location: Ylistönrinne, YAA303

M.Sc. Kanoktip Puttaraksa defends her doctoral dissertation in Cell and Molecular Biology ”Pathogenic mechanisms of how human parvovirus breaks self-tolerance”. Opponent  Associate Professor, Docent Nancy C.Horton (University of Arizona, USA) and custos Professor Adjunct Professor Leona Gilbert (University of Jyväskylä).

Kanoktip Puttaraksa
Kanoktip Puttaraksa

Viruses are known to involve in the development of autoimmune diseases; however, their functions and mechanisms remain unclear. The aim of this research is to explore pathologic mechanisms of how viral infections initiate autoimmunity, an immune response against our own tissues, by using a common human parvovirus B19 (B19V) as a study model. The multifunctional non-structural protein 1 (NS1), a member of superfamily 3 (SF3) helicase, of B19V has been demonstrated to initiate host’s DNA damage, which leads to a programmed cell death known as apoptosis. It is hypothesized that NS1 is the key contributor to proceed from B19V infections to autoimmune conditions. In this thesis, the effects of B19V NS1 on the host’s cells and immune system have been investigated. Results of this research revealed that apoptotic cells induced by B19V NS1 created apoptotic bodies (ApoBods), which contained NS1 protein and host’s cellular components. Therefore, immune responses initiated by B19V NS1-induced ApoBods were studied. Biological and immunological aspects of B19V NS1-induced ApoBods were examined in laboratory immune cell assays, animal experiments, as well as patient samples analysis. It was demonstrated that ApoBods induced by B19V NS1 stimulate immune cells to produce multiple immune reactions. Furthermore, immunization of B19V NS1-induced ApoBods was illustrated to contribute in the activation of autoimmune conditions in non-autoimmune mice, which indicated by the production of anti-dsDNA autoantibodies and development of autoimmune conditions in major organs such as glomerulonephritis in kidneys. In addition, it was found that antibodies against NS1 protein were detected at high level in B19V acute and chronic patients; whereas, antibodies against NS1-induced ApoBods were detected at high level in

chronic B19V patients with autoimmune conditions. As a result, NS1 protein and NS1-induced ApoBods were indicated as worthy antigens for examination of acute, chronic, and autoimmuneassociated with B19V infections.

In summary, this research exhibited that B19V regulate the conditions from infections to autoimmune disorders through NS1 functions in the activation of apoptosis and formation of ApoBods. B19V NS1- induced ApoBods were specified as the potential inducer of autoimmune diseases. Moreover, inhibition of viral helicase protein, such as NS1 of B19V, could be the target for the new antiviral treatment to prevent chronic infectious diseases that eventually leads to initiate autoimmune diseases. Keywords: Autoimmunity; apoptosis; apoptotic bodies; autoantibodies; human parvovirus B19; nonstructural protein 1; self-antigens.

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Kanoktip Puttaraksa