Human cytomegalovirus (hCMV) is a ubiquitous latent persistent herpesvirus infecting 60–90% of the population worldwide. hCMV carriage in immunocompetent people is asymptomatic; thus, hCMV can be considered a component of normative aging. However, hCMV powerfully modulates many features of the immune, and likely other, systems and organs. Questions remain as to how hCMV carriage affects the human host. We used anti-CMV antibody titers as a stratifying criterion to examine the impact of “intensity” of hCMV infection as a potential biomarker of aging, inflammation, and immune homeostasis in a cohort of 247 participants stratified into younger (21–40 years) and older (> 65 years of age) groups. We showed that anti-CMV antibody titers increased with age and directly correlated to increased levels of soluble tumor necrosis factor (sTNFR) I in younger but not older participants. CD8 + cell numbers were reduced in the older group due to the loss in CD8 + T naïve (Tn) cells. In CMV carriers and, in particular, in anti-CMV Ab-high participants, this loss was mitigated or reversed by an increase in the numbers of CD8 + T effector memory (Tem) and T effector memory reexpressing CD45RA (Temra) cells. Analysis of CD38, HLA-DR, and CD57 expression revealed subset (CD4 or CD8)-specific changes that correlated with anti-CMV Ab levels. In addition, anti-CMV Ab levels predicted anti-CMV CD8 T cell responsiveness to different CMV open reading frames (ORFs) selectively in older participants, which correlated to the transcriptional order of expression of specific CMV ORFs. Implications of these results for the potential predictive value of anti-CMV Ab titers during aging are discussed.

人类巨细胞病毒 (hCMV) 是一种普遍存在的潜伏性持续性疱疹病毒，感染全球 60-90% 的人口。免疫功能正常的人携带 hCMV 是无症状的；因此，hCMV 可以被认为是正常衰老的一个组成部分。然而，hCMV 可以强有力地调节免疫系统和器官以及可能的其他系统和器官的许多特征。 hCMV 携带如何影响人类宿主仍存在疑问。我们使用抗 CMV 抗体滴度作为分层标准，在 247 名参与者的队列中检查 hCMV 感染“强度”作为衰老、炎症和免疫稳态的潜在生物标志物的影响，该队列被分层为年轻（21-40 岁）和年龄较大（> 65 岁）群体。我们发现，在年轻参与者中，抗 CMV 抗体滴度随着年龄的增长而增加，并且与可溶性肿瘤坏死因子 (sTNFR) I 水平的增加直接相关，但与老年参与者无关。由于 CD8 + T 幼稚 (Tn) 细胞的损失，老年组中 CD8 + 细胞数量减少。在 CMV 携带者中，特别是在抗 CMV Ab 高参与者中，这种损失通过 CD8 + T 效应记忆 (Tem) 和重新表达 CD45RA (Temra) 细胞的数量增加而减轻或逆转。 CD38、HLA-DR 和 CD57 表达的分析揭示了与抗 CMV Ab 水平相关的子集（CD4 或 CD8）特异性变化。此外，抗CMV抗体水平预测老年参与者中抗CMV CD8 T细胞对不同CMV开放阅读框（ORF）的选择性反应，这与特定CMV ORF表达的转录顺序相关。讨论了这些结果对衰老过程中抗 CMV 抗体滴度的潜在预测价值的影响。