Monocytes Latently Infected with Human Cytomegalovirus Evade Neutrophil Killing.
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Elder, E., Krishna, B., Williamson, J., Aslam, Y., Farahi, N., Wood, A., Romashova, V., et al. (2019). Monocytes Latently Infected with Human Cytomegalovirus Evade Neutrophil Killing.. iScience, 12 13-26. https://doi.org/10.1016/j.isci.2019.01.007
It is now well established that one site of latency of human cytomegalovirus (HCMV) in vivo is in undifferentiated cells of the myeloid lineage, including monocytes and their CD34+ progenitors. Although latently infected cells are known to evade host T cell responses by suppression of T cell effector functions, it is not known if they also have to actively evade surveillance by other host immune cells. Here we show cells latently infected with HCMV can, indeed, be killed by host neutrophils but only in a serum-dependent manner. Specifically, antibodies to the viral latency-associated US28 protein can mediate neutrophil killing of latently infected cells. This begs the question as to how latently infected cells avoid such neutrophil targeting. To address this, a full proteomic screen was carried out on monocytes latently infected with HCMV which showed that the neutrophil chemoattractants S100A8/A9 are robustly downregulated in latently infected monocytes thereby suppressing neutrophil recruitment to these latently infected cells. This ability of cells latently infected with HCMV to inhibit neutrophil recruitment represents a novel immune evasion strategy of this persistent human pathogen, preventing clearance of the latent viral reservoir.
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
External DOI: https://doi.org/10.1016/j.isci.2019.01.007
This record's URL: https://www.repository.cam.ac.uk/handle/1810/288701
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/