Immediate Early Interactions and Epigenetic Defense Mechanisms
Qiyi Tang and Gerd G. Maul
from: Cytomegaloviruses: Molecular Biology and Immunology (Edited by: Matthias J. Reddehase). Caister Academic Press, U.K. (2006)
Abstract
This article reviews the very early temporal, sequential and spatial choreography of cytomegalovirus attack and the host's defenses. It begins with the apparent paradox that viral genomes are deposited to nuclear domains (ND10), which due to their interferon upregulated components appear involved in nuclear defenses. The defenses are described as attempts to silence the immediate early promoter by histone deacetylation. Viral counter measures appear to be an increasing production of the immediate early protein (IE1), which binds and thus inactivates the histone deacetylases thus maintaining the immediate early promoter open for transcription. Additional paradoxes such as the simultaneous production of IE1 as a phenotypic activator and the immediate early protein 2 as a suppressor from the same transcript are considered as are the unexpected positioning of the immediate early promoter within the highest concentration of its own repressor without being repressed. Possible resolutions to these paradoxes appear in a sequence of protein interactions, which suggest that temporal inactivation takes place by segregation. This segregation provides the possibility that transactivating viral proteins are maintained and can become active upon as yet unknown signals that change the balance in an individual infected cell between suppression and eventual resolution of infection or progression to successful and lytic replication. This balance also contains the promise that it can be shifted, possibly by small molecules interacting with viral proteins thus rendering them ineffective like deletion mutants read more ...
