Circumstantial evidence argues that the ongoing stimulation of the immune system during CMV latency may prompt or aggravate the course of chronic inflammatory conditions, such as atherosclerosis or diabetes. This idea has been compounded by the distinct tropism of latent CMV infection for endothelial cells or stromal cells, as well as for immune cells of the myeloid lineage. Unfortunately, the evidence has remained correlative and largely based on retrospective studies, which were unable to determine if HCMV infection and immunity is a consequence of underlying conditions (e.g. genetic susceptibility of the host to infections), or the cause of immune responses that aggravate the chronic clinical conditions.

The Čičin-Šain lab has been at the front of studies on immune imprinting by CMV infection for the past ten years. We have demonstrated by experimental evidence a causative role of CMV infection in the life-long persistence of strong T-cell based immune responses (Čičin-Šain et al. 2012). We have also identified the role of antigen expression (Dekhtiarenko et al. 2013), processing (Dekhtiarenko et al. 2016), and TCR-mediated recognition on MHC molecules (Borkner et al. 2017) in the inflation of memory responses against CMV antigens in the latently infected host. More recently, we have shown that the obsession of the immune system with HCMV does not affect the ability of the host to respond and control numerous other viral infections (Marandu et al. 2015), but rather that CMV infection induces a persistent inflammation of adipose tissues due to a viral persistence in non-hematopoietic cells in the fat tissue (Contreras et al. 2019). We have now expanded our technical expertise to the study of primary human lymphocytes, and to the identification of HCMV genomes in human cell subsets. The availability of the senior cohort of older adults will allow us to identify the functionality of HCMV specific T cells late in life.