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Early slowdown of the peripheral immune response triggered by Puumala virus infection

Pathogenic hantaviruses in Europe cause hemorrhagic fever with renal syndrome (HFRS). They significantly differ by their pathogenicity resulting in broad spectra of clinical presentations. Infections with hantaviruses are not lytic, and it is still not clear 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 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 searched. Methods: Using real-time PCR array technology, the relative expression of immune response genes and miRNAs was measured in peripheral blood mononuclear cells of patients infected with Puumala virus (PUUV). Results: The results showed down regulation of 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 differential 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. Conclusions: The results showed initial suppression of the early immune response to PUUV which was more pronounced in more severe form of the disease.

hantavirus; HFRS; innate immunity; gene expression; PBMC

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