Human cytomegalovirus (HCMV) is a highly prevalent pathogen that induces life-long infections notably through the establishment of latency in hematopoietic stem cells (HSC). Bouts of reactivation are normally controlled by the immune system, but can be fatal in immuno-compromised individuals such as organ transplant recipients. Here, we reveal that HCMV latency in human CD34(+) HSC reflects the recruitment on the viral genome of KAP1, a master co-repressor, together with HP1 and the SETDB1 histone methyltransferase, which results in transcriptional silencing. During lytic infection, KAP1 is still associated with the viral genome, but its heterochromatin-inducing activity is suppressed by mTOR-mediated phosphorylation. Correspondingly, HCMV can be forced out of latency by KAP1 knockdown or pharmacological induction of KAP1 phosphorylation, and this process can be potentiated by activating NFkB with TNF-α. These results suggest new approaches both to curtail CMV infection and to purge the virus from organ transplants.
Release of human cytomegalovirus from latency by a KAP1/TRIM28 phosphorylation switch / B. Rauwel, S. Jang, M. Cassano, A. Kapopoulou, I. Barde, D. Trono. - In: ELIFE. - ISSN 2050-084X. - 2015:4(2015 Apr), pp. e06068.1-e06068.20.
|Titolo:||Release of human cytomegalovirus from latency by a KAP1/TRIM28 phosphorylation switch|
|Parole Chiave:||cytomegalovirus; epigenetics; hematopoietic stem cells; human; infectious disease; microbiology|
|Settore Scientifico Disciplinare:||Settore BIO/17 - Istologia|
|Data di pubblicazione:||apr-2015|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.7554/eLife.06068|
|Appare nelle tipologie:||01 - Articolo su periodico|