Reeves, M;
Jackson, S;
Wills, M;
Groves, I;
Chen, K;
Okecha, G;
Sinclair, J;
... Houldcroft, C; + view all
(2021)
Latent cytomegalovirus-driven recruitment of activated CD4+ T cells promotes virus reactivation.
Frontiers in Immunology
10.3389/fimmu.2021.657945.
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Abstract
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.
| Type: | Article |
|---|---|
| Title: | Latent cytomegalovirus-driven recruitment of activated CD4+ T cells promotes virus reactivation |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fimmu.2021.657945 |
| Publisher version: | https://doi.org/10.3389/fimmu.2021.657945 |
| Language: | English |
| Additional information: | © 2021 Jackson, Chen, Groves, Sedikides, Gandhi, Houldcroft, Poole, Montanuy, Mason, Okecha, Reeves, Sinclair and Wills. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10125252 |
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