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Monocytes Latently Infected with Human Cytomegalovirus Evade Neutrophil Killing.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Krishna, Benjamin Anthony Cates  ORCID logo  https://orcid.org/0000-0003-0919-2961
Aslam, Yusuf 
Farahi, Neda 

Abstract

One site of latency of human cytomegalovirus (HCMV) in vivo is in undifferentiated cells of the myeloid lineage. 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 must also evade surveillance by other host immune cells. Here we show that 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 mediate neutrophil killing of latently infected cells. To address this mechanistically, a full proteomic screen was carried out on latently infected monocytes. This showed that latent infection downregulates the neutrophil chemoattractants S100A8/A9, thus suppressing neutrophil recruitment to latently infected cells. The ability of latently infected cells to inhibit neutrophil recruitment represents an immune evasion strategy of this persistent human pathogen, helping to prevent clearance of the latent viral reservoir.

Description

Keywords

Immune Response, Immunology, Molecular Mechanism of Behavior, Virology

Journal Title

iScience

Conference Name

Journal ISSN

2589-0042
2589-0042

Volume Title

12

Publisher

Elsevier BV
Sponsorship
Medical Research Council (G0701279)
Medical Research Council (MR/K021087/1)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (MR/S00081X/1)
Wellcome Trust (099790/Z/12/Z)
Wellcome Trust (210688/Z/18/Z)