New cell-signaling pathways for controlling cytomegalovirus replication.
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.
Department of Pediatrics, Division of Infectious Diseases, Johns Hopkins University School of Medicine, Baltimore, MD.
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D000263:Adenylate Kinase / Q000378:metabolism; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D003587:Cytomegalovirus / Q000502:physiology*; D004249:DNA Damage; D006801:Humans; D059748:Proteolysis; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D025801:Ubiquitin; D056811:Unfolded Protein Response; D014779:Virus Replication; D051153:Wnt Proteins / Q000378:metabolism
D025801:Ubiquitin; D051153:Wnt Proteins; C546842:MTOR protein, human; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D058570:TOR Serine-Threonine Kinases; D000263:Adenylate Kinase
AMPK; ATM; CMV; Wnt; mTOR; signal transduction