New cell-signaling pathways for controlling cytomegalovirus replication

Abstract

Cytomegalovirus (CMV) is increasingly recognized as an accomplished modulator of cell-signaling pathways, both directly via interaction between viral and cellular proteins, and indirectly by activating metabolic/energy states of infected cells. Viral genes, as well as captured cellular genes, enable CMV to modify these pathways upon binding to cellular receptors, up until generation of virus progeny. Deregulation of cell-signaling pathways appears to be a well-developed tightly balanced virus strategy to achieve the desired consequences in each infected cell type. Importantly and perhaps surprisingly, identification of new signaling pathways in cancer cells positioned CMV as a sophisticated user and abuser of many such pathways, creating opportunities to develop novel therapeutic strategies for inhibiting CMV replication (in addition to standard of care CMV DNA polymerase inhibitors). Advances in genomics and proteomics allow the identification of CMV products interacting with the cellular machinery. Ultimately, clinical implementation of candidate drugs capable of disrupting the delicate balance between CMV and cell-signaling will depend on the specificity and selectivity index of newly identified targets. Modulation of cell-signaling pathways by cytomegalovirus is an important viral strategy for survival and infectivity, and mechanistic studies of these pathways may lead to the development of compounds with high selectivity against virus replication. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.