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Mitogen and Stress Activated Kinases Act Co-operatively with CREB during the Induction of Human Cytomegalovirus Immediate-Early Gene Expression from Latency


Human cytomegalovirus (HCMV) infection of immune-compromised individuals is a significant cause of morbidity. In a number of settings disease is caused by the reactivation of a pre-existing quiescent infection of the host (latency) which, in the absence of a controlling immune response, is a major source of disease. Work to understand the switch from a latent to active (reactivated) infection has focussed on the regulation of the promoter that controls the major viral gene products IE72 and IE86 – an important first step towards HCMV reactivation. In this study we have correlated the activation of cellular signalling pathways with the downstream activation of this promoter. Specifically, the activation of cellular kinase in an ERK-MAPK dependent manner which displays an affinity for a protein bound to a key viral promoter drives a change in the chromatin architecture that allows viral gene expression – releasing the virus from the latent state.


Vyšlo v časopise: Mitogen and Stress Activated Kinases Act Co-operatively with CREB during the Induction of Human Cytomegalovirus Immediate-Early Gene Expression from Latency. PLoS Pathog 10(6): e32767. doi:10.1371/journal.ppat.1004195
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004195

Souhrn

Human cytomegalovirus (HCMV) infection of immune-compromised individuals is a significant cause of morbidity. In a number of settings disease is caused by the reactivation of a pre-existing quiescent infection of the host (latency) which, in the absence of a controlling immune response, is a major source of disease. Work to understand the switch from a latent to active (reactivated) infection has focussed on the regulation of the promoter that controls the major viral gene products IE72 and IE86 – an important first step towards HCMV reactivation. In this study we have correlated the activation of cellular signalling pathways with the downstream activation of this promoter. Specifically, the activation of cellular kinase in an ERK-MAPK dependent manner which displays an affinity for a protein bound to a key viral promoter drives a change in the chromatin architecture that allows viral gene expression – releasing the virus from the latent state.


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