Journal
CELL REPORTS
Volume 38, Issue 10, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2022.110469
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Funding
- HPI Strategic Incentive Program
- Leibniz Science Campus InterACt [W6/2018]
- Free and Hanseatic City of Hamburg
- Deutsche Forschungsgemeinschaft (DFG) (German Research Foundation) under Germany's Excellence Strategy EXC [390874280]
- Wellcome Trust [209250/Z/17/Z, FOR5200(BO4158/5-1)]
- German Center for Infection Research (DZIF)
- Federal Ministry of Health
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Human cytomegalovirus forms replication compartments in the host cell nucleus using liquid-liquid phase separation with specific proteins, ensuring efficient viral genome replication.
Human cytomegalovirus (HCMV) replicates its DNA genome in specialized replication compartments (RCs) in the host cell nucleus. These membrane-less organelles originate as spherical structures and grow in size over time. However, the mechanism of RC biogenesis has remained understudied. Using live-cell imaging and photo-oligomerization, we show that a central component of RCs, the UL112-113 proteins, undergo liquid liquid phase separation (LLPS) to form RCs in the nucleus. We show that the self-interacting domain and large intrinsically disordered regions of UL112-113 are required for LLPS. Importantly, viral DNA induces local clustering of these proteins and lowers the threshold for phase separation. The formation of phase-separated compartments around viral genomes is necessary to recruit the viral DNA polymerase for viral genome replication. Thus, HCMV uses its UL112-113 proteins to generate RCs around viral genomes by LLPS to ensure the formation of a pro-replicative environment.
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