Cytomegalovirus and the aging population

Human cytomegalovirus (HCMV) has the largest genome of any virus known to infect man. The virus has evolved many strategies to manipulate the host immune systems and so can remain latent and evade important immune responses. The human host mounts a substantial immune response against the virus, with up to 1% of the virus-specific CD8+ T cells being directed against specific epitopes. Acquisition of HCMV occurs progressively from an early age, and in developed countries the overall seroprevalence is approximately 60%. In contrast, specific communities such as gay men, lower socioeconomic groups and people residing in developing countries have seroprevalence rates that can exceed 90%. It is a widely held belief that successful control of viral infections decreases with increasing age because of a reduction in the capacity of the immune system. Studies in aging populations have shown a specific expansion of the CD8+, CD28- and CD57+ subset of cells in patients who are HCMV-seropositive. Prior infection with HCMV has also been associated with a significantly increased number of CD4+ and CD8+ lymphocytes, as well as cells expressing CD56 and HLA-DR. Thus, HCMV infection can cause substantial perturbations in T cell subsets and these effects persist in the aging population. In the context of solid organ transplantation, older age of both recipients and donors may serve to increase the frequency of donor-positive recipient-positive (D+R+) transplants, which have only a moderate risk of HCMV disease. In the context of HIV infection, age has been a dominant risk factor for progression to AIDS and death. At present, it does not appear that this can be explained by lack of immune control of HCMV in the aging population, although studies have identified prior HCMV infection as a risk factor for AIDS and death independent of age. We await further investigations to determine whether the immune control of HCMV in the elderly patient is as effective as in the younger adult, and whether this is linked to pathological consequences.