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Human Cytomegalovirus Upregulates Expression of HCLS1 Resulting in Increased Cell Motility and Transendothelial Migration during Latency

Human cytomegalovirus establishes a lifelong, latent infection in the human host and can cause significant morbidity and mortality, particularly, in immunocompromised individuals. One established site of HCMV latency and reactivation is in cells of the myeloid lineage. In undifferentiated myeloid ce...

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Autores principales: Aslam, Yusuf, Williamson, James, Romashova, Veronika, Elder, Elizabeth, Krishna, Benjamin, Wills, Mark, Lehner, Paul, Sinclair, John, Poole, Emma
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817630/
https://www.ncbi.nlm.nih.gov/pubmed/31569051
http://dx.doi.org/10.1016/j.isci.2019.09.016
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author Aslam, Yusuf
Williamson, James
Romashova, Veronika
Elder, Elizabeth
Krishna, Benjamin
Wills, Mark
Lehner, Paul
Sinclair, John
Poole, Emma
author_facet Aslam, Yusuf
Williamson, James
Romashova, Veronika
Elder, Elizabeth
Krishna, Benjamin
Wills, Mark
Lehner, Paul
Sinclair, John
Poole, Emma
author_sort Aslam, Yusuf
collection PubMed
description Human cytomegalovirus establishes a lifelong, latent infection in the human host and can cause significant morbidity and mortality, particularly, in immunocompromised individuals. One established site of HCMV latency and reactivation is in cells of the myeloid lineage. In undifferentiated myeloid cells, such as CD14+ monocytes, virus is maintained latently. We have recently reported an analysis of the total proteome of latently infected CD14+ monocytes, which identified an increase in hematopoietic lineage cell-specific protein (HCLS1). Here we show that this latency-associated upregulation of HCLS1 occurs in a US28-dependent manner and stabilizes actin structure in latently infected cells. This results in their increased motility and ability to transit endothelial cell layers. Thus, latency-associated increases in monocyte motility could aid dissemination of the latently infected reservoir, and targeting this increased motility could have an impact on the ability of latently infected monocytes to distribute to tissue sites of reactivation.
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spelling pubmed-68176302019-10-31 Human Cytomegalovirus Upregulates Expression of HCLS1 Resulting in Increased Cell Motility and Transendothelial Migration during Latency Aslam, Yusuf Williamson, James Romashova, Veronika Elder, Elizabeth Krishna, Benjamin Wills, Mark Lehner, Paul Sinclair, John Poole, Emma iScience Article Human cytomegalovirus establishes a lifelong, latent infection in the human host and can cause significant morbidity and mortality, particularly, in immunocompromised individuals. One established site of HCMV latency and reactivation is in cells of the myeloid lineage. In undifferentiated myeloid cells, such as CD14+ monocytes, virus is maintained latently. We have recently reported an analysis of the total proteome of latently infected CD14+ monocytes, which identified an increase in hematopoietic lineage cell-specific protein (HCLS1). Here we show that this latency-associated upregulation of HCLS1 occurs in a US28-dependent manner and stabilizes actin structure in latently infected cells. This results in their increased motility and ability to transit endothelial cell layers. Thus, latency-associated increases in monocyte motility could aid dissemination of the latently infected reservoir, and targeting this increased motility could have an impact on the ability of latently infected monocytes to distribute to tissue sites of reactivation. Elsevier 2019-09-14 /pmc/articles/PMC6817630/ /pubmed/31569051 http://dx.doi.org/10.1016/j.isci.2019.09.016 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aslam, Yusuf
Williamson, James
Romashova, Veronika
Elder, Elizabeth
Krishna, Benjamin
Wills, Mark
Lehner, Paul
Sinclair, John
Poole, Emma
Human Cytomegalovirus Upregulates Expression of HCLS1 Resulting in Increased Cell Motility and Transendothelial Migration during Latency
title Human Cytomegalovirus Upregulates Expression of HCLS1 Resulting in Increased Cell Motility and Transendothelial Migration during Latency
title_full Human Cytomegalovirus Upregulates Expression of HCLS1 Resulting in Increased Cell Motility and Transendothelial Migration during Latency
title_fullStr Human Cytomegalovirus Upregulates Expression of HCLS1 Resulting in Increased Cell Motility and Transendothelial Migration during Latency
title_full_unstemmed Human Cytomegalovirus Upregulates Expression of HCLS1 Resulting in Increased Cell Motility and Transendothelial Migration during Latency
title_short Human Cytomegalovirus Upregulates Expression of HCLS1 Resulting in Increased Cell Motility and Transendothelial Migration during Latency
title_sort human cytomegalovirus upregulates expression of hcls1 resulting in increased cell motility and transendothelial migration during latency
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817630/
https://www.ncbi.nlm.nih.gov/pubmed/31569051
http://dx.doi.org/10.1016/j.isci.2019.09.016
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