Journal Article

PUBDB-2024-00343

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Human cytomegalovirus forms phase-separated compartments at viral genomes to facilitate viral replication

Caragliano, E.CSSB* ; Bonazza, S. ; Frascaroli, G. ; Tang, J. ; Soh, T. K.Extern*CSSB* ; Grünewald, K.CSSB*DESY* ; Bosse, J. B. (Corresponding author)Extern*CSSB* ; Brune, W. (Corresponding author)

2022
Elsevier [New York, NY]

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Please use a persistent id in citations: doi:10.1016/j.celrep.2022.110469  doi:10.3204/PUBDB-2024-00343

Abstract: 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.

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Contributing Institute(s):

1. CSSB-MHH-JB (CSSB-MHH-JB)
2. CSSB - Leibniz-Institut für Experimentelle Virologie (LIV) - Kay Grünewald (CSSB-LIV-KG)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)
2. DFG project 390874280 - EXC 2155: RESIST - Resolving Infection Susceptibility (390874280) (390874280)

Experiment(s):

1. No specific instrument

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