Stalemating a clever opportunist: lessons from murine cytomegalovirus

Cytomegaloviruses and their specific hosts have come to an arrangement that avoids disease but allows the viruses to persist in the individual host and to spread in the host species. Recent work has uncovered some of the molecular details of this evolutionary "contract for mutual survival." Cytomegaloviruses encode proteins, referred to as "immunoevasins," which are specifically committed to subvert the immune defense of the host for evading virus elimination. In reply, the hosts have evolved countermeasures to overcome the viral immunoevasins and present antigenic peptides to an extent that is sufficient for confining virus replication to below a harmful level. Accordingly, cytomegalic inclusion disease is a disease only of the immunocompromised. Although the details of the contract differ between the various cytomegalovirus host pairs, the general principles are strikingly analogous. Paradigmatic findings were made in the murine model, which adds the advantage of providing proof of principle by in vivo studies. With the focus on CD8 T cells and the major histocompatibility complex class I pathway of antigen presentation, we will discuss our view on the immune surveillance of cytomegalovirus in the murine model.