The immunoregulatory effects of CMV-infection in human fibroblasts and the impact on cellular senescence

We observed that CMV-infection led to the induction of several immunoregulatory host cell genes associated with the innate and adaptive immune system. These were genes of different function such as genes regulating apoptosis, cytokines/chemokines and genes that are responsible for the detection of pathogens. Some of the genes upregulated following CMV-infection are also upregulated during cellular senescence, indicating that CMV causes an immunological phenotype in fibroblasts, which is partially reminiscent of replicative senescent cells.In summary our results demonstrate that CMV not only affects the T cell pool but also induces inflammatory processes in human fibroblasts.Cytomegalovirus (CMV) is a ubiquitous beta-herpesvirus with a worldwide prevalence of 60-100% in the adult population [1]. Infection occurs early and leads to life-long persistence in the host. CMV is one of the most immunodominant antigens and stimulates immune responses of unprecedented magnitude [2]. Several studies have shown that latent infection with cytomegalovirus contributes to age-related alterations of the immune system, particularly of the T cell compartment as it drives the differentiation of T cells and accelerates immunosenescence [3]. In the human host CMV exhibits tropism among others for monocytes/macrophages, fibroblasts and endothelial cells [4-6]. Previous reports demonstrate that CMV induces premature senescence in early passage human fibroblasts. Similar to senescent cells, which have reached the limit of their replicative capacity [7], CMV-infected fibroblasts show intense senescence-associated ？-Galactosidase (SA-？-gal) activity and increased mRNA expression of the cell cycle arrest gene p16 [8,9]. Replicatively senescent fibroblasts characteristically also produce increased levels of inflammatory molecules [10]. They may thus contribute to the development of subclinical age-related inflammatory processes ('inflamm-aging') [11] and are believed to support the development