TY - JOUR
AU - Caragliano, Enrico
AU - Bonazza, Stefano
AU - Frascaroli, Giada
AU - Tang, Jiajia
AU - Soh, Timothy K.
AU - Grünewald, Kay
AU - Bosse, Jens Bernhard
AU - Brune, Wolfram
TI - Human cytomegalovirus forms phase-separated compartments at viral genomes to facilitate viral replication
JO - Cell reports
VL - 38
IS - 10
SN - 2211-1247
CY - [New York, NY]
PB - Elsevier
M1 - PUBDB-2024-00343
SP - 110469
PY - 2022
AB - SummaryHuman 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.
LB - PUB:(DE-HGF)16
C6 - pmid:35263605
UR - <Go to ISI:>//WOS:000768295500003
DO - DOI:10.1016/j.celrep.2022.110469
UR - https://bib-pubdb1.desy.de/record/601650
ER -