TY - JOUR TI - Release of human cytomegalovirus from latency by a KAP1/TRIM28 phosphorylation switch AU - Rauwel, Benjamin AU - Jang, Suk Min AU - Cassano, Marco AU - Kapopoulou, Adamandia AU - Barde, Isabelle AU - Trono, Didier A2 - Sinclair, John VL - 4 PY - 2015 DA - 2015/04/07 SP - e06068 C1 - eLife 2015;4:e06068 DO - 10.7554/eLife.06068 UR - https://doi.org/10.7554/eLife.06068 AB - 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. KW - epigenetic KW - hematopoietic stem cell KW - cytomegalovirus JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -