Latent Cytomegalovirus-Driven Recruitment of Activated CD4+ T Cells Promotes Virus Reactivation.
Chen, Kevin C
Sedikides, George X
Mason, Gavin M
Reeves, Matthew B
Frontiers Media SA
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Jackson, S., Chen, K. C., Groves, I., Sedikides, G. X., Gandhi, A., Houldcroft, C., Poole, E., et al. (2021). Latent Cytomegalovirus-Driven Recruitment of Activated CD4+ T Cells Promotes Virus Reactivation.. Front Immunol, 12 657945. https://doi.org/10.3389/fimmu.2021.657945
Human cytomegalovirus (HCMV) infection is not cleared by the initial immune response but persists for the lifetime of the host, in part due to its ability to establish a latent infection in cells of the myeloid lineage. HCMV has been shown to manipulate the secretion of cellular proteins during both lytic and latent infection; with changes caused by latent infection mainly investigated in CD34+ progenitor cells. Whilst CD34+ cells are generally bone marrow resident, their derivative CD14+ monocytes migrate to the periphery where they briefly circulate until extravasation into tissue sites. We have analyzed the effect of HCMV latent infection on the secretome of CD14+ monocytes, identifying an upregulation of both CCL8 and CXCL10 chemokines in the CD14+ latency-associated secretome. Unlike CD34+ cells, the CD14+ latency-associated secretome did not induce migration of resting immune cell subsets but did induce migration of activated NK and T cells expressing CXCR3 in a CXCL10 dependent manner. As reported in CD34+ latent infection, the CD14+ latency-associated secretome also suppressed the anti-viral activity of stimulated CD4+ T cells. Surprisingly, however, co-culture of activated autologous CD4+ T cells with latently infected monocytes resulted in reactivation of HCMV at levels comparable to those observed using M-CSF and IL-1β cytokines. We propose that these events represent a potential strategy to enable HCMV reactivation and local dissemination of the virus at peripheral tissue sites.
B-Lymphocytes, T-Lymphocytes, Monocytes, Humans, Cytomegalovirus, Cytomegalovirus Infections, Cytokines, Lymphocyte Activation, Virus Latency, Virus Replication, Virus Activation, Chemotaxis, Leukocyte, Biomarkers
Medical Research Council (G0701279)
Medical Research Council (MR/K021087/1)
Medical Research Council (MR/S00081X/1)
External DOI: https://doi.org/10.3389/fimmu.2021.657945
This record's URL: https://www.repository.cam.ac.uk/handle/1810/319123
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