The impact of Cytomegalovirus on the human immune system

Since it was first noted in the 1880s, Cytomegalovirus (CMV) has shown that it has the capacity to infect a lot of different cell types and organs. However in the immunocompetent host, it may infect asymptomatically, and only when the immune system is impaired does it show its potential for damage. CMV is known as an important cause of congenital infections, and is the leading cause of such. Furthermore, the virus can be transmitted from the mother following reactivation, even when she has protective immunity against it. Although the majority of babies recover intact, it can leave important sequelae, like deafness and mental retardation. CMV is also a scourge of the immunocompromised, as became clear from the first organ transplants in the 1970's, with the growing number of solid organ transplants, combined with immunosupressive therapy to avoid organ rejection. It was often observed that fulminant CMV infections developed within 10 days of the transplant, frequently leading to organ rejection. With the advent of the AIDS epidemic in the early '80s, fulminant CMV infections were often among the serious symptoms observed when the patients' immune system was comprised.
A little later, CMV's influence on T cells in the elderly was investigated (Looney, '99), and soon afterward, it was incorporated into the Immune Risk Phenotype (IRP) profile to identify persons with elevated risk of mortality over the next few years (Whitby 2000). Given the potential to cause trouble, it is imperative to know CMV and its mechanisms better. The SardiNIA project (Pilia 2006), a large, longitudinal cross-sectional study of the population of the Lanusei valley, provides a way to glean further detail on CMV and its impact on the ageing immune system.
As such, we have performed high-definition characterization by FACS analysis of a large number of persons in the project (Orrù 2013). This has allowed the study to go beyond white blood cell counts to deconstruct leukocytes into a large number of distinct sub-populations and quantify them. The panels were designed to examine a number of important immune cell populations. By serological testing we have determined CMV status of the participants. Our work is to monitor the roles of CMV status together with sex and age to have a detailed description of immunoageing in the SardiNIA dataset.

Members:
Michael Bernard Whalen (Principal investigator)