Study of natural killer lymphocytes transcriptionally reprogrammed by vaccinia virus Vaccinia Virus NKK mCMV biorxivpreprint Cambridge_Uni fredhutch
Studies have reported that NK lymphocytes play a crucial role in controlling poxvirus infections. Therefore, there is a growing scientific interest in exploiting their abilities in terms of poxvirus-based oncolytic therapies and vaccinations. However, data on the mechanisms of NK cell activation, receptors involved in recognizing VACV-infected lymphocytes, and the ways of reprogramming NK lymphocytes as a result of VACV infections are limited.
Subsequently, the changes were compared to identical NK lymphocyte transcriptomic data from modified vaccinia Ankara -infected humans and cytomegalovirus -infected C57BL/6 mice. Further, the transcriptional profiles of NK lymphocytes were compared with flow cytometry-determined cell surface molecule abundance. Fluorescence-activated cell sorting analysis and lymphocyte isolation experiments were performed.
Twenty-eight days post intradermal VACV infection, blood and spleen samples were obtained from mice. Splenic tissues were used for NK or cluster of differentiation 8+ T lymphocyte isolation. The tail veils of recipient murine animals were intravenously injected with NK lymphocytes, CD8+ T lymphocytes, or suspensions of splenocytes, and the mice were intranasally challenged with 105 PFU of VACV WR after one day.
DEGs in VACV-infected murine animals at 1.5 dpi could not be distinguished from background noises, whereas those identified in the infected animals at 6.5 dpi differed biologically in their responses to VACV infections. NK lymphocytes engaged effector pathways and displayed active defense phenotypes resulting from VACV infections.
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