Overview of clinical and molecular aspects involved in the development of symptomatic infection and end-organ disease caused by cytomegalovirus in pediatric patients

The use of immunosuppressive drugs in patients with cancer, development of new therapies as solid organ transplant (SOT) or bone marrow transplantation (BMT), viral infections such as Human Immunodeficiency Virus (HIV), haematological malignancy and prematurity in newborns, are factors that carry an immunosuppression state, which increase the host susceptibility to develop cytomegalovirus active infection (CMV-AI) either by reactivation or primary infection. Once the CMV-AI has been established, some patients develop symptomatic infection (SI) and end-organ-disease (EOD), while others remain asymptomatic. This suggests that in the host-pathogen interaction, there are factors from both that are involved in the risk of symptomatic infection and subsequent complications following AI. Some of them have been analyzed from a molecular viewpoint and their role in clinical behaviour is well known. However, others are still unclear, and several investigations are evaluating its possible role in pathogenesis. In this chapter, we will review and discuss the molecular basis and clinical aspects in pediatric patients involved as risk factors to develop SI and EOD following CMV-AI. Among them: the ability to evade the immune response, the emergence of mutants with antiviral resistance, genotypic variants and multiple infection, the ability of the virus to modulate cell signalling mechanisms, Donor/Receptor serology (D/R) in patients with SOT and BMT, the mechanisms of immune alterations induced by HIV and lack of immune response due to prematurity status in newborns, as potential factors involved in the risk of symptomatic infection and EOD in SOT, BMT, HIV infection, patients with haematological disorders and preterm newborn, following IA. We also are discussing the influence of the mentioned factors in subsequent complications as bacterial or fungal infections, which can eventually have an important role in a fatal outcome.