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The expression level changes of lineage-specific cell surface molecules on innate immune cells in response to orthohantavirus infection

Introduction: Puumala and Tula orthohantavirus are enveloped RNA viruses, belonging to genus Orthohantavirus (HTV), family Hantaviridae, order Bunyavirales. Puumala orthohantavirus (PUUV) is pathogenic causing mild to moderate forms of hemorrhagic fever with renal syndrome in Euroasia while Tula orthohantavirus (TULV) is considered apathogenic due to limited evidence of pathogenesis in humans. Monocytes, macrophages and dendritic cells (DC), as innate immune system cells, are target cells for HTV potentially contributing to dissemination of the virus in the body and development of the disease. There is still a lack of knowledge about the mechanisms of immune response to HTV. The aim of this in vitro study was to analyze the expression dymanics of the selected cell surface molecules on monocytes, macrophages and DC infected with PUUV or TULV in order to investigate whether orthohantavirus infection triggers differentiation and subsequent cell polarization. Materials and Methods: Primary human monocytes were infected in vitro with PUUV or TULV and cultured for seven days post infection. Immunophenotyping was done in three time points using in-house created polychromatic screening panel with antibodies specific for surface molecules on monocytes, macrophages and DC. After staining and fixation, samples acquisition was performed on a Navios flow cytometer (Beckman Coulter, USA). Data files were analysed using FlowLogic software (Inivai Technologies, Australia). Results: The expression levels of lineage-specific (monocyte, macrophage and DC) cell surface molecules between orthohantavirus infected cells and mock infection were different, as well as between pathogenic and apathogenic infections. Conclusion: Orthohantaviruses induce differentiation of primary human monocytes as seen at the level of cell surface markers expression. Differences are observed between pathogenic and apathogenic orthohantaviruses infections.

primary human monocytes, macrophages, dendritic cells, immunophenotyping

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