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Cytomegalovirus viral load within blood increases markedly in healthy people over the age of 70 years

BACKGROUND: Cytomegalovirus (CMV) is a highly prevalent herpesvirus, which maintains lifelong latency and places a significant burden on host immunity. Infection is associated with increased rates of vascular disease and overall mortality in the elderly and there is an urgent need for improved under...

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Autores principales: Parry, Helen M., Zuo, Jianmin, Frumento, Guido, Mirajkar, Nikhil, Inman, Charlotte, Edwards, Emma, Griffiths, Mike, Pratt, Guy, Moss, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700608/
https://www.ncbi.nlm.nih.gov/pubmed/26734066
http://dx.doi.org/10.1186/s12979-015-0056-6
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author Parry, Helen M.
Zuo, Jianmin
Frumento, Guido
Mirajkar, Nikhil
Inman, Charlotte
Edwards, Emma
Griffiths, Mike
Pratt, Guy
Moss, Paul
author_facet Parry, Helen M.
Zuo, Jianmin
Frumento, Guido
Mirajkar, Nikhil
Inman, Charlotte
Edwards, Emma
Griffiths, Mike
Pratt, Guy
Moss, Paul
author_sort Parry, Helen M.
collection PubMed
description BACKGROUND: Cytomegalovirus (CMV) is a highly prevalent herpesvirus, which maintains lifelong latency and places a significant burden on host immunity. Infection is associated with increased rates of vascular disease and overall mortality in the elderly and there is an urgent need for improved understanding of the viral-host balance during ageing. CMV is extremely difficult to detect in healthy donors, however, using droplet digital PCR of DNA from peripheral blood monocytes, we obtained an absolute quantification of viral load in 44 healthy donors across a range of ages. RESULTS: Viral DNA was detected in 24 % (9/37) of donors below the age of 70 but was found in all individuals above this age. Furthermore, the mean CMV load was only 8.6 copies per 10,000 monocytes until approximately 70 years of age when it increased by almost 30 fold to 249 copies in older individuals (p < 0.0001). CMV was found within classical CD14+ monocytes and was not detectable within the CD14-CD16+ subset. The titre of CMV-specific IgG increased inexorably with age indicating that loss of humoral immunity is not a determinant of the increased viral load. In contrast, although cellular immunity to the structural late protein pp65 increased with age, the T cell response to the immediate early protein IE1 decreased in older donors. CONCLUSION: These data reveal that effective control of CMV is impaired during healthy ageing, most probably due to loss of cellular control of early viral reactivation. This information will be of value in guiding efforts to reduce CMV-associated health complications in the elderly. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12979-015-0056-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-47006082016-01-06 Cytomegalovirus viral load within blood increases markedly in healthy people over the age of 70 years Parry, Helen M. Zuo, Jianmin Frumento, Guido Mirajkar, Nikhil Inman, Charlotte Edwards, Emma Griffiths, Mike Pratt, Guy Moss, Paul Immun Ageing Research BACKGROUND: Cytomegalovirus (CMV) is a highly prevalent herpesvirus, which maintains lifelong latency and places a significant burden on host immunity. Infection is associated with increased rates of vascular disease and overall mortality in the elderly and there is an urgent need for improved understanding of the viral-host balance during ageing. CMV is extremely difficult to detect in healthy donors, however, using droplet digital PCR of DNA from peripheral blood monocytes, we obtained an absolute quantification of viral load in 44 healthy donors across a range of ages. RESULTS: Viral DNA was detected in 24 % (9/37) of donors below the age of 70 but was found in all individuals above this age. Furthermore, the mean CMV load was only 8.6 copies per 10,000 monocytes until approximately 70 years of age when it increased by almost 30 fold to 249 copies in older individuals (p < 0.0001). CMV was found within classical CD14+ monocytes and was not detectable within the CD14-CD16+ subset. The titre of CMV-specific IgG increased inexorably with age indicating that loss of humoral immunity is not a determinant of the increased viral load. In contrast, although cellular immunity to the structural late protein pp65 increased with age, the T cell response to the immediate early protein IE1 decreased in older donors. CONCLUSION: These data reveal that effective control of CMV is impaired during healthy ageing, most probably due to loss of cellular control of early viral reactivation. This information will be of value in guiding efforts to reduce CMV-associated health complications in the elderly. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12979-015-0056-6) contains supplementary material, which is available to authorized users. BioMed Central 2016-01-05 /pmc/articles/PMC4700608/ /pubmed/26734066 http://dx.doi.org/10.1186/s12979-015-0056-6 Text en © Parry et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Parry, Helen M.
Zuo, Jianmin
Frumento, Guido
Mirajkar, Nikhil
Inman, Charlotte
Edwards, Emma
Griffiths, Mike
Pratt, Guy
Moss, Paul
Cytomegalovirus viral load within blood increases markedly in healthy people over the age of 70 years
title Cytomegalovirus viral load within blood increases markedly in healthy people over the age of 70 years
title_full Cytomegalovirus viral load within blood increases markedly in healthy people over the age of 70 years
title_fullStr Cytomegalovirus viral load within blood increases markedly in healthy people over the age of 70 years
title_full_unstemmed Cytomegalovirus viral load within blood increases markedly in healthy people over the age of 70 years
title_short Cytomegalovirus viral load within blood increases markedly in healthy people over the age of 70 years
title_sort cytomegalovirus viral load within blood increases markedly in healthy people over the age of 70 years
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4700608/
https://www.ncbi.nlm.nih.gov/pubmed/26734066
http://dx.doi.org/10.1186/s12979-015-0056-6
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