Modulation of T-Cell mediated immunity by cytomegalovirus

Abstract

The herpesviruses have coevolved with their vertebrate hosts for over one hundred million years (McGeoch et al. 2000), resulting in a finely tuned equilibrium with the immune system. Consequently, all herpesviruses employ a multitude of strategies to modulate the host immune response, facilitating the establishment of lifelong latency and/or persistence in the face of a robust innate and adaptive immune response. Cytomegalovirus (CMV, a β-herpesvirus) is the largest of the herpesviruses, with a genome of ∼230 kB in size encoding >200 open reading frames (orfs). Approximately ∼60% of the encoded genes are not essential for replication of virus in tissue culture where there is no selective pressure from the host immune system and are predicted to perform immunomodulatory functions and facilitate establishment of latency (Murphy et al. 2003; Brocchieri et al. 2005). CMV directly targets dendritic cells (DC) and exploits the DC's crucial role in the regulation of innate and adaptive anti-viral immune responses to promote replication and establish latency while preventing host pathology.