We describe how the interaction of HCMV with neutrophils triggers a profound survival phenotype that involves ERK phosphorylation and IκB degradation and correlates with MCL-1 stabilization, along with the secretion of a bioactive secretome that promotes further neutrophil survival, monocyte chemotaxis, and development of monocyte permissiveness for HCMV infection. Here, MCL1 is linked to cytomegalovirus infection.