Sara van den Berg

193 7 Duration of CMV infection Figure 6. Model of establishment of the size of the immune response to control latent CMV infection. Both establishment of the viral latent reservoir after primary infection (1) and the subsequent viral reactivation in time (2) will affect the CMV-specific immune response. Different factors may influence both phases; those based on our data are presented in black rectangles. Figure created with Biorender.com. In fact, elderly individuals with high CMV-specific antibody levels and high numbers of CMV-specific T EMRA cells could also be the ones who were more recently infected with CMV. While we confirmed that CMV infection is related to cardiovascular disease, we found limited evidence for a relationship with general health i.e. frailty. We therefore propose an alternative hypothesis that high CMV-specific immune responses in elderly may not be a cause of poor health outcomes, but may instead be a sign of impaired health status. ACKNOWLEDGEMENTS We thank Irina Tcherniaeva, Marjan Bogaard-van Maurik, Ronald Jacobi and Gerco den Hartog for help with the CMV serology and Petra Vissink for the longitudinal samples of the DCS.

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