Skip to main content
Top
Published in: Immunity & Ageing 1/2014

Open Access 01-12-2014 | Research

Molecular mechanisms associated with the strength of the anti-CMV response in nonagenarians

Authors: Saara Marttila, Juulia Jylhävä, Laura Kananen, Antti Hervonen, Marja Jylhä, Mikko Hurme

Published in: Immunity & Ageing | Issue 1/2014

Login to get access

Abstract

Background

Infection with human cytomegalovirus (CMV) affects the function and composition of the immune system during ageing. In addition to the presence of the pathogen, the strength of the immune response, as measured by the anti-CMV IgG titre, has a significant effect on age-related pathogenesis. High anti-CMV IgG titres have been associated with increased mortality and functional impairment in the elderly. In this study, we were interested in identifying the molecular mechanisms that are associated with the strength of the anti-CMV response by examining the gene expression profiles that are associated with the level of the anti-CMV IgG titre.

Results

The level of the anti-CMV IgG titre is associated with the expression level of 663 transcripts in nonagenarians. These transcripts and their corresponding pathways are, for the most part, associated with metabolic functions, cell development and proliferation and other basic cellular functions. However, no prominent associations with the immune system were found, and no associated transcripts were found in young controls.

Conclusions

The lack of defence pathways associated with the strength of the anti-CMV response can indicate that the compromised immune system can no longer defend itself against the CMV infection. Our data imply that the association between high anti-CMV IgG titres and increased mortality and frailty is mediated by basic cellular processes.
Appendix
Available only for authorised users
Literature
1.
go back to reference Pawelec G, McElhaney JE, Aiello AE, Derhovanessian E: The impact of CMV infection on survival in older humans. Curr Opin Immunol. 2012, 24: 507-511. 10.1016/j.coi.2012.04.002.CrossRefPubMed Pawelec G, McElhaney JE, Aiello AE, Derhovanessian E: The impact of CMV infection on survival in older humans. Curr Opin Immunol. 2012, 24: 507-511. 10.1016/j.coi.2012.04.002.CrossRefPubMed
2.
go back to reference Looney RJ, Falsey A, Campbell D, Torres A, Kolassa J, Brower C, McCann R, Menegus M, McCormick K, Frampton M, Hall W, Abraham GN: Role of cytomegalovirus in the T cell changes seen in elderly individuals. Clin Immunol. 1999, 90: 213-219. 10.1006/clim.1998.4638.CrossRefPubMed Looney RJ, Falsey A, Campbell D, Torres A, Kolassa J, Brower C, McCann R, Menegus M, McCormick K, Frampton M, Hall W, Abraham GN: Role of cytomegalovirus in the T cell changes seen in elderly individuals. Clin Immunol. 1999, 90: 213-219. 10.1006/clim.1998.4638.CrossRefPubMed
3.
go back to reference Chidrawar S, Khan N, Wei W, McLarnon A, Smith N, Nayak L, Moss P: Cytomegalovirus-seropositivity has a profound influence on the magnitude of major lymphoid subsets within healthy individuals. Clin Exp Immunol. 2009, 155: 423-432. 10.1111/j.1365-2249.2008.03785.x.PubMedCentralCrossRefPubMed Chidrawar S, Khan N, Wei W, McLarnon A, Smith N, Nayak L, Moss P: Cytomegalovirus-seropositivity has a profound influence on the magnitude of major lymphoid subsets within healthy individuals. Clin Exp Immunol. 2009, 155: 423-432. 10.1111/j.1365-2249.2008.03785.x.PubMedCentralCrossRefPubMed
4.
go back to reference Derhovanessian E, Maier AB, Beck R, Jahn G, Hähnel K, Slagboom PE, de Craen AJM, Westendorp RGJ, Pawelec G: Hallmark features of immunosenescence are absent in familial longevity. J Immunol. 2010, 185: 4618-4624. 10.4049/jimmunol.1001629.CrossRefPubMed Derhovanessian E, Maier AB, Beck R, Jahn G, Hähnel K, Slagboom PE, de Craen AJM, Westendorp RGJ, Pawelec G: Hallmark features of immunosenescence are absent in familial longevity. J Immunol. 2010, 185: 4618-4624. 10.4049/jimmunol.1001629.CrossRefPubMed
5.
go back to reference Lachmann R, Bajwa M, Vita S, Smith H, Cheek E, Akbar A, Kern F: Polyfunctional T cells accumulate in large human cytomegalovirus-specific T cell responses. J Virol. 2012, 86: 1001-1009. 10.1128/JVI.00873-11.PubMedCentralCrossRefPubMed Lachmann R, Bajwa M, Vita S, Smith H, Cheek E, Akbar A, Kern F: Polyfunctional T cells accumulate in large human cytomegalovirus-specific T cell responses. J Virol. 2012, 86: 1001-1009. 10.1128/JVI.00873-11.PubMedCentralCrossRefPubMed
6.
go back to reference Kuparinen T, Marttila S, Jylhävä J, Tserel L, Peterson P, Jylhä M, Hervonen A, Hurme M: Cytomegalovirus (CMV)-dependent and -independent changes in the aging of the human immune system: a transcriptomic analysis. Exp Gerontol. 2013, 48: 305-312. 10.1016/j.exger.2012.12.010.CrossRefPubMed Kuparinen T, Marttila S, Jylhävä J, Tserel L, Peterson P, Jylhä M, Hervonen A, Hurme M: Cytomegalovirus (CMV)-dependent and -independent changes in the aging of the human immune system: a transcriptomic analysis. Exp Gerontol. 2013, 48: 305-312. 10.1016/j.exger.2012.12.010.CrossRefPubMed
7.
go back to reference Strandberg TE, Pitkala KH, Tilvis RS: Cytomegalovirus antibody level and mortality among community-dwelling older adults with stable cardiovascular disease. JAMA. 2009, 301: 380-382.CrossRefPubMed Strandberg TE, Pitkala KH, Tilvis RS: Cytomegalovirus antibody level and mortality among community-dwelling older adults with stable cardiovascular disease. JAMA. 2009, 301: 380-382.CrossRefPubMed
8.
go back to reference Roberts ET, Haan MN, Dowd JB, Aiello AE: Cytomegalovirus antibody levels, inflammation, and mortality among elderly Latinos over 9 years of follow-up. Am J Epidemiol. 2010, 172: 363-371. 10.1093/aje/kwq177.PubMedCentralCrossRefPubMed Roberts ET, Haan MN, Dowd JB, Aiello AE: Cytomegalovirus antibody levels, inflammation, and mortality among elderly Latinos over 9 years of follow-up. Am J Epidemiol. 2010, 172: 363-371. 10.1093/aje/kwq177.PubMedCentralCrossRefPubMed
9.
go back to reference Gkrania-Klotsas E, Langenberg C, Sharp SJ, Luben R, Khaw KT, Wareham NJ: Seropositivity and higher immunoglobulin g antibody levels against cytomegalovirus are associated with mortality in the population-based European prospective investigation of cancer-norfolk cohort. Clin Infect Dis. 2013, 56: 1421-1427. 10.1093/cid/cit083.PubMedCentralCrossRefPubMed Gkrania-Klotsas E, Langenberg C, Sharp SJ, Luben R, Khaw KT, Wareham NJ: Seropositivity and higher immunoglobulin g antibody levels against cytomegalovirus are associated with mortality in the population-based European prospective investigation of cancer-norfolk cohort. Clin Infect Dis. 2013, 56: 1421-1427. 10.1093/cid/cit083.PubMedCentralCrossRefPubMed
10.
go back to reference Savva GM, Pachnio A, Kaul B, Morgan K, Huppert FA, Brayne C, Moss PA, Medical Research Council Cognitive Function and Ageing Study: Cytomegalovirus infection is associated with increased mortality in the older population. Aging Cell. 2013, 13: 381-387.CrossRef Savva GM, Pachnio A, Kaul B, Morgan K, Huppert FA, Brayne C, Moss PA, Medical Research Council Cognitive Function and Ageing Study: Cytomegalovirus infection is associated with increased mortality in the older population. Aging Cell. 2013, 13: 381-387.CrossRef
11.
go back to reference Haarala A, Kähönen M, Lehtimäki T, Aittoniemi J, Jylhävä J, Hutri-Kähönen N, Taittonen L, Laitinen T, Juonala M, Viikari J, Raitakari OT, Hurrme M: Relation of high cytomegalovirus antibody titres to blood pressure and brachial artery flow-mediated dilation in young men: the cardiovascular risk in young Finns study. Clin Exp Immunol. 2012, 167: 309-316. 10.1111/j.1365-2249.2011.04513.x.PubMedCentralCrossRefPubMed Haarala A, Kähönen M, Lehtimäki T, Aittoniemi J, Jylhävä J, Hutri-Kähönen N, Taittonen L, Laitinen T, Juonala M, Viikari J, Raitakari OT, Hurrme M: Relation of high cytomegalovirus antibody titres to blood pressure and brachial artery flow-mediated dilation in young men: the cardiovascular risk in young Finns study. Clin Exp Immunol. 2012, 167: 309-316. 10.1111/j.1365-2249.2011.04513.x.PubMedCentralCrossRefPubMed
12.
go back to reference Wang GC, Kao WH, Murakami P, Xue QL, Chiou RB, Detrick B, McDyer JF, Semba RD, Casolaro V, Walston JD, Fried LP: Cytomegalovirus infection and the risk of mortality and frailty in older women: a prospective observational cohort study. Am J Epidemiol. 2010, 171: 1144-1152. 10.1093/aje/kwq062.PubMedCentralCrossRefPubMed Wang GC, Kao WH, Murakami P, Xue QL, Chiou RB, Detrick B, McDyer JF, Semba RD, Casolaro V, Walston JD, Fried LP: Cytomegalovirus infection and the risk of mortality and frailty in older women: a prospective observational cohort study. Am J Epidemiol. 2010, 171: 1144-1152. 10.1093/aje/kwq062.PubMedCentralCrossRefPubMed
13.
go back to reference Moro-García MA, Alonso-Arias R, López-Vázquez A, Suárez-García FM, Solano-Jaurrieta JJ, Baltar J, López-Larrea C: Relationship between functional ability in older people, immune system status, and intensity of response to CMV. Age. 2012, 34: 479-495. 10.1007/s11357-011-9240-6.PubMedCentralCrossRefPubMed Moro-García MA, Alonso-Arias R, López-Vázquez A, Suárez-García FM, Solano-Jaurrieta JJ, Baltar J, López-Larrea C: Relationship between functional ability in older people, immune system status, and intensity of response to CMV. Age. 2012, 34: 479-495. 10.1007/s11357-011-9240-6.PubMedCentralCrossRefPubMed
14.
go back to reference Aiello AE, Haan MN, Pierce CM, Simanek AM, Liang J: Persistent infection, inflammation, and functional impairment in older Latinos. J Gerontol A Biol Sci Med Sci. 2008, 63: 610-618. 10.1093/gerona/63.6.610.PubMedCentralCrossRefPubMed Aiello AE, Haan MN, Pierce CM, Simanek AM, Liang J: Persistent infection, inflammation, and functional impairment in older Latinos. J Gerontol A Biol Sci Med Sci. 2008, 63: 610-618. 10.1093/gerona/63.6.610.PubMedCentralCrossRefPubMed
15.
go back to reference Matheï C, Vaes B, Wallemacq P, Degryse J: Associations between cytomegalovirus infection and functional impairment and frailty in the BELFRAIL Cohort. J Am Geriatr Soc. 2011, 59: 2201-2208. 10.1111/j.1532-5415.2011.03719.x.CrossRefPubMed Matheï C, Vaes B, Wallemacq P, Degryse J: Associations between cytomegalovirus infection and functional impairment and frailty in the BELFRAIL Cohort. J Am Geriatr Soc. 2011, 59: 2201-2208. 10.1111/j.1532-5415.2011.03719.x.CrossRefPubMed
16.
go back to reference Alonso Arias R, Moro-García MA, Echeverría A, Solano-Jaurrieta JJ, Suárez-García FM, López-Larrea C: Intensity of the humoral response to cytomegalovirus is associated with the phenotypic and functional status of the immune system. J Virol. 2013, 87: 4486-4495. 10.1128/JVI.02425-12.PubMedCentralCrossRefPubMed Alonso Arias R, Moro-García MA, Echeverría A, Solano-Jaurrieta JJ, Suárez-García FM, López-Larrea C: Intensity of the humoral response to cytomegalovirus is associated with the phenotypic and functional status of the immune system. J Virol. 2013, 87: 4486-4495. 10.1128/JVI.02425-12.PubMedCentralCrossRefPubMed
17.
go back to reference Li D, Zheng L, Jin L, Zhou Y, Li H, Fu J, Shi M, Du P, Wang L, Wu H, Chen GY, Zheng P, Liu Y, Wang FS, Wang S: CD24 polymorphisms affect risk and progression of chronic hepatitis B virus infection. Hepatology. 2009, 50: 735-742. 10.1002/hep.23047.CrossRefPubMed Li D, Zheng L, Jin L, Zhou Y, Li H, Fu J, Shi M, Du P, Wang L, Wu H, Chen GY, Zheng P, Liu Y, Wang FS, Wang S: CD24 polymorphisms affect risk and progression of chronic hepatitis B virus infection. Hepatology. 2009, 50: 735-742. 10.1002/hep.23047.CrossRefPubMed
18.
go back to reference Qi Y, Mao ZQ, Ruan Q, He R, Ma YP, Sun ZR, Ji YH, Huang Y: Human cytomegalovirus (HCMV) UL139 open reading frame: Sequence variants are clustered into three major genotypes. J Med Virol. 2006, 78: 517-522. 10.1002/jmv.20571.CrossRefPubMed Qi Y, Mao ZQ, Ruan Q, He R, Ma YP, Sun ZR, Ji YH, Huang Y: Human cytomegalovirus (HCMV) UL139 open reading frame: Sequence variants are clustered into three major genotypes. J Med Virol. 2006, 78: 517-522. 10.1002/jmv.20571.CrossRefPubMed
19.
go back to reference Yang SH, Sharrocks AD, Whitmarsh AJ: MAP kinase signalling cascades and transcriptional regulation. Gene. 2013, 513: 1-13. 10.1016/j.gene.2012.10.033.CrossRefPubMed Yang SH, Sharrocks AD, Whitmarsh AJ: MAP kinase signalling cascades and transcriptional regulation. Gene. 2013, 513: 1-13. 10.1016/j.gene.2012.10.033.CrossRefPubMed
20.
go back to reference Moon JS, Lee MY, Park SW, Han WK, Hong SW, Ahn JH, Kim KS: Androgen-dependent activation of human cytomegalovirus major immediate-early promoter in prostate cancer cells. Prostate. 2008, 68: 1450-1460. 10.1002/pros.20817.CrossRefPubMed Moon JS, Lee MY, Park SW, Han WK, Hong SW, Ahn JH, Kim KS: Androgen-dependent activation of human cytomegalovirus major immediate-early promoter in prostate cancer cells. Prostate. 2008, 68: 1450-1460. 10.1002/pros.20817.CrossRefPubMed
21.
22.
go back to reference Pagliaccetti NE, Robek MD: Interferon-λ the immune response to hepatitis B virus and hepatitis C virus. J Interferon Cytokine Res. 2010, 30: 585-590. 10.1089/jir.2010.0060.PubMedCentralCrossRefPubMed Pagliaccetti NE, Robek MD: Interferon-λ the immune response to hepatitis B virus and hepatitis C virus. J Interferon Cytokine Res. 2010, 30: 585-590. 10.1089/jir.2010.0060.PubMedCentralCrossRefPubMed
23.
go back to reference Brand S, Beigel F, Olszak T, Zitzmann K, Eichhorst ST, Otte JM, Diebold J, Diepolder H, Adler B, Auernhammer CJ, Göke B, Dambacher J: IL-28A and IL-29 mediate antiproliferative and antiviral signals in intestinal epithelial cells and murine CMV infection increases colonic IL-28A expression. Am J Physiol Gastrointest Liver Physiol. 2005, 289: G960-G968. 10.1152/ajpgi.00126.2005.CrossRefPubMed Brand S, Beigel F, Olszak T, Zitzmann K, Eichhorst ST, Otte JM, Diebold J, Diepolder H, Adler B, Auernhammer CJ, Göke B, Dambacher J: IL-28A and IL-29 mediate antiproliferative and antiviral signals in intestinal epithelial cells and murine CMV infection increases colonic IL-28A expression. Am J Physiol Gastrointest Liver Physiol. 2005, 289: G960-G968. 10.1152/ajpgi.00126.2005.CrossRefPubMed
24.
go back to reference Goebeler S, Jylhä M, Hervonen A: Medical history, cognitive status and mobility at the age of 90: a population-based study in Tampere, Finland. Aging Clin Exp Res. 2003, 15: 154-161. 10.1007/BF03324494.CrossRefPubMed Goebeler S, Jylhä M, Hervonen A: Medical history, cognitive status and mobility at the age of 90: a population-based study in Tampere, Finland. Aging Clin Exp Res. 2003, 15: 154-161. 10.1007/BF03324494.CrossRefPubMed
25.
go back to reference Tiainen K, Hurme M, Hervonen A, Luukkaala T, Jylhä M: Inflammatory markers and physical performance among nonagenarians. J Gerontol A Biol Sci Med Sci. 2010, 65: 658-663.CrossRefPubMed Tiainen K, Hurme M, Hervonen A, Luukkaala T, Jylhä M: Inflammatory markers and physical performance among nonagenarians. J Gerontol A Biol Sci Med Sci. 2010, 65: 658-663.CrossRefPubMed
26.
go back to reference Kallio MA, Tuimala JT, Hupponen T, Klemelä P, Gentile M, Scheinin I, Koski M, Käki J, Korpelainen EI: Chipster: user-friendly analysis software for microarray and other high-throughput data. BMC Genomics. 2011, 12: 507-10.1186/1471-2164-12-507.PubMedCentralCrossRefPubMed Kallio MA, Tuimala JT, Hupponen T, Klemelä P, Gentile M, Scheinin I, Koski M, Käki J, Korpelainen EI: Chipster: user-friendly analysis software for microarray and other high-throughput data. BMC Genomics. 2011, 12: 507-10.1186/1471-2164-12-507.PubMedCentralCrossRefPubMed
Metadata
Title
Molecular mechanisms associated with the strength of the anti-CMV response in nonagenarians
Authors
Saara Marttila
Juulia Jylhävä
Laura Kananen
Antti Hervonen
Marja Jylhä
Mikko Hurme
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Immunity & Ageing / Issue 1/2014
Electronic ISSN: 1742-4933
DOI
https://doi.org/10.1186/1742-4933-11-2

Other articles of this Issue 1/2014

Immunity & Ageing 1/2014 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine