Evidence for the Role of Cyclic AMP-Responsive Elements in Human Virus Replication and Disease

We review the involvement of the cyclic AMP responsive DNA element (CRE) and the ATF/CREB (activating transcription factor/CRE binding protein) family of transcription factors in the regulation and pathology of clinically important viruses that infect humans, including the herpesviridae, adenoviridae, parvoviridae, hepadnaviridae, and retroviridae families. CRE sequences found in specific regulatory elements of human viruses are listed, and the functional evidence for CRE activity, in the form of DNA binding assays, mutational studies, transfection and transcriptional activation experiments, or in vitro transcription assays, is summarized. Manipulation of cellular processes is required for virus replication in human cells following infection. A primary target of many viruses is the cellular transcription machinery, and several human viruses contain transcriptional activator and repressor proteins that affect cellular transcription. Through their effect on cellular transcription, viral genes alter the pattern of cellular gene expression, and thereby affect the differentiation state and cell cycle progression of the infected cell. We summarize evidence demonstrating that the CRE and its binding proteins are involved in the activity of the viruses, implicating their function in the pathogenesis of human diseases. The targeting of specific transcription factor pathways as a potential therapeutic approach is discussed. Copyright 1996 S. Karger AG, Basel