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Cytomegalovirus and Epstein-Barr virus co-infected young and middle-aged adults can have an aging-related T-cell phenotype.

ABSTRACT: Cytomegalovirus (CMV) is known to alter circulating effector memory or re-expressing CD45RA⁺ (TemRA) T-cell numbers, but whether Epstein-Barr virus (EBV) does the same or this is amplified during a CMV and EBV co-infection is unclear. Immune cell numbers in blood of children and young, middle-aged, and senior adults (n = 336) were determined with flow cytometry, and additional multivariate linear regression, intra-group correlation, and cluster analyses were performed. Compared to non-infected controls, CMV-seropositive individuals from all age groups had more immune cell variance, and CMV⁺ EBV^- senior adults had more late-differentiated CD4⁺ and CD8⁺ TemRA and CD4⁺ effector memory T-cells. EBV-seropositive children and young adults had a more equal immune cell composition than non-infected controls, and CMV^- EBV⁺ senior adults had more intermediate/late-differentiated CD4⁺ TemRA and effector memory T-cells than non-infected controls. CMV and EBV co-infected young and middle-aged adults with an elevated BMI and anti-CMV antibody levels had a similar immune cell composition as senior adults, and CMV⁺ EBV⁺ middle-aged adults had more late-differentiated CD8⁺ TemRA, effector memory, and HLA-DR⁺ CD38^- T-cells than CMV⁺ EBV^- controls. This study identified changes in T-cell numbers in CMV- or EBV-seropositive individuals and that some CMV and EBV co-infected young and middle-aged adults had an aging-related T-cell phenotype.

SUBMITTER: Hofstee MI

PROVIDER: S-EPMC10322942 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Cytomegalovirus and Epstein-Barr virus co-infected young and middle-aged adults can have an aging-related T-cell phenotype.

Hofstee Marloes I MI Cevirgel Alper A de Zeeuw-Brouwer Mary-Lène ML de Rond Lia L van der Klis Fiona F Buisman Anne-Marie AM

Scientific reports 20230705 1

Cytomegalovirus (CMV) is known to alter circulating effector memory or re-expressing CD45RA<sup>+</sup> (TemRA) T-cell numbers, but whether Epstein-Barr virus (EBV) does the same or this is amplified during a CMV and EBV co-infection is unclear. Immune cell numbers in blood of children and young, middle-aged, and senior adults (n = 336) were determined with flow cytometry, and additional multivariate linear regression, intra-group correlation, and cluster analyses were performed. Compared to non ...[more]

PMID: 37407603

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Project description:BackgroundChronological aging-associated changes in the human DNA methylome have been studied by multiple epigenome-wide association studies (EWASs). Certain CpG sites have been identified as aging-associated in multiple studies, and the majority of the sites identified in various studies show common features regarding location and direction of the methylation change. However, as a whole, the sets of aging-associated CpGs identified in different studies, even with similar tissues and age ranges, show only limited overlap. In this study, we further explore and characterize CpG sites that show close relationship between their DNA methylation level and chronological age during adulthood and which bear the relationship regardless of blood cell type heterogeneity.ResultsIn this study, with a multivariable regression model adjusted for cell type heterogeneity, we identified 1202 aging-associated CpG sites (a-CpGs, FDR < 5%), in whole blood in a population with an especially narrow age range (40 - 49 years). Repeatedly reported a-CpGs located in genes ELOVL2, FHL2, PENK and KLF14 were also identified. Regions with aging-associated hypermethylation were enriched regarding several gene ontology (GO) terms (especially in the cluster of developmental processes), whereas hypomethylated sites showed no enrichment. The genes with higher numbers of a-CpG hits were more often hypermethylated with advancing age. The comparison analysis revealed that of the 1202 a-CpGs identified in the present study, 987 were identified as differentially methylated also between nonagenarians and young adults in a previous study (The Vitality 90+ study), and importantly, the directions of changes were identical in the previous and in the present study.ConclusionsHere we report that aging-associated DNA methylation features can be identified in a middle-aged population with an age range of only 9 years. A great majority of these sites have been previously reported as aging-associated in a population aged 19 to 90 years. Aging is associated with different types of changes in DNA methylation, clock-like as well as random. We speculate that the a-CpGs identified here in a population with a narrow age-range represent clock-like changes, as they showed concordant methylation behavior in population spanning whole adulthood as well.

Dataset Information

Cytomegalovirus and Epstein-Barr virus co-infected young and middle-aged adults can have an aging-related T-cell phenotype.

Publications

Cytomegalovirus and Epstein-Barr virus co-infected young and middle-aged adults can have an aging-related T-cell phenotype.

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