The Mouse Cytomegalovirus Glycoprotein m155 Inhibits CD40

Cytomegaloviruses (CMV) utilize a variety of immunomodulatory strategies to facilitate the establishment of lifelong persistence in their infected hosts. We show that the mouse CMV (MCMV) m155 open reading frame (ORF) is required for the posttranscriptional inhibition of CD40 expression in infected antigen-presenting cells. Consistent with the known importance of CD40-mediated costimulation of T cells, a m155-deficient virus induces enhanced MCMV epitope-specific CD4 T cell responses. Healthy individuals infected with human cytomegalovirus (HCMV) are largely asymptomatic, but HCMV infection can result in high morbidity and death in immunosuppressed pa-tients (12, 38, 48). HCMV establishes lifelong persistence, which is thought to require manipulation of the host’s immune system by the coordinated function of many viral immuno-modulatory genes (34). As adaptive immune responses develop during infection, interactions occur between mature antigen-presenting cells (APC) and their cognate T cells. The quality and quantity o