In vivo impact of cytomegalovirus evasion of CD8 T-cell immunity: facts and thoughts based on murine models

Abstract

Cytomegaloviruses (CMVs) co-exist with their respective host species and have evolved to avoid their elimination by the hosts' immune effector mechanisms and to persist in a non-replicative state, known as viral latency. There is evidence to suggest that latency is nevertheless a highly dynamic condition during which episodes of viral gene desilencing, which can be viewed as incomplete reactivations, cause intermittent antigenic activity that stimulates CD8 memory-effector T cells and drives their clonal expansion. These T cells are supposed to terminate reactivation before completion of the productive viral cycle. In this view, CMVs do not "evade" their respective host's immune response but are actually held in check all the time, unless the host gets immunocompromised. Accordingly, CMV disease is typically a disease of the immunocompromised host only. Here we review current knowledge about the in vivo role of viral proteins involved in subverting the immune recognition of infected cells with focus on the CD8 T-cell response and viral interference with the MHC class-I pathway of antigenic peptide presentation. Whereas the intracellular functions of these "immune-evasion proteins" are known in molecular detail, knowledge of their in vivo role in CMV biology is only beginning to take shape. Experimental studies on the in vivo function of human CMV (hCMV) immune-evasion proteins prohibits, of course. Studying animal CMVs paradigmatically in the corresponding natural host is therefore used to identify principles from which the role of hCMV immune-evasion proteins can hopefully be inferred. Here we summarize recent insights gained primarily from the murine model.