DNA Sensors' Signaling in NK Cells During HHV-6A, HHV-6B and HHV-7 Infection

Frontiers in Microbiology
Daria BortolottiRoberta Rizzo

Abstract

The host DNA sensor proteins TLR9, STING, IFI16 are central signaling molecules that control the innate immune response to cytosolic nucleic acids. Here we propose to investigate how Natural killer (NK) cell infection by human herpesvirus (HHV)-6A, HHV-6B or HHV-7 is able to modify DNA sensor signaling in NK cells. We infected the NK92 cell line and primary NK cells with cell-free inocula of HHV-6A, HHV-6B or HHV-7 and evaluated TLR9, STING, and IFI16 pathway expression by Real-Time PCR, Western Blot, immunofluorescence and flow cytometry for 1, 2, 3, and 6 days post-infection. We evaluated NK cell cytokine-producing by Real-Time PCR and enzyme immunosorbent assay. NK92 and primary NK cells were promptly infected by three viruses, as demonstrated by virus presence (DNA) and transcription (RNA) analysis. Our data show STING/STAT6 up-modulation in HHV-6A infected NK cells. NK cells infected with HHV-6B and HHV-7 up-regulated CCL3, IFN-alpha, TNF-alpha, IL-8 and IFN-gamma and slightly induced IL-4, and CCL4. HHV-6A infected NK cells up-regulated IL-4 and IL-13 and slightly induced IL-10, TNF-alpha, IFN-alpha, and IFN-gamma. For the first time, we demonstrate that HHV-6A, HHV-6B, and HHV-7 infections have a differential impact on i...Continue Reading

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Citations

Apr 13, 2021·Frontiers in Immunology·Anthony L KomaroffJeffrey L Ecker
Jul 25, 2021·International Journal of Molecular Sciences·Daniel G SausenRonen Borenstein

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Methods Mentioned

BETA
FCS
flow cytometry
PCR
enzyme-linked immunosorbent assays

Software Mentioned

FlowJo
Graph pad

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