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.

Contribution of viral and bacterial infections to senescence and immunosenescence

“…Additionally, it has been reported that EBV-infected B cells trigger a G1 cellular arrest phase and exhibit augmented markers of OIS, such as H3K9me3 senescence-associated heterochromatic foci, p16, p21 and p53 in ( Nikitin et al., 2010 ; Nikitin et al., 2014 ; McFadden et al., 2016 ) ( Figure 2 ). Recently, it has been reported that co-infection with EBV and HCMV in young and middle-aged adults can alter T cell composition towards an aging-related T cell phenotype ( Hofstee et al., 2023 ).…”