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Early immunoreactins in peripheral blood mononuclear cells induced by Puumala virus

Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS). Infections with hantaviruses are not lytic, and it is currently unknown why infections in humans cause the disease. It is considered that pathogenesis of HFRS is mainly mediated by immune response. The aim of this study was to explore the components of innate and adaptive immunity important in the early peripheral immune response as well as the possible regulatory effect of miRNA on early immunoreactions during the hantaviral infection. Based on this, biological pathways relevant for the immunopathogenesis of HFRS have also been defined. Using real-time PCR array technology, the relative expression of immune response genes and miRNA was measured in peripheral blood mononuclear cells of patients infected with Puumala virus (PUUV). The results showed suppression of the early immune response to PUUV i.e. genes coding the synthesis of pattern recognition receptors, chemokines and their receptors, cytokines, transcription factors, as well as some signalling molecules. Functional analysis showed that down regulation of the expression of described set of genes modulates inflammatory response by interfering with various cell-signalling pathways. For the first time, the biological importance of miRNA in the regulation of immune response during HFRS was shown. Changes detected at the immune response level have been associated with disease severity but not with the viral load in the blood.

hantaviruses; Puumala virus; miRNA expression; immune response; hemorrhagic fever with renal syndrome

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