Human cytomegalovirus forms phase-separated compartments at viral genomes to facilitate viral replication
Summary: 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. Usin...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-03-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124722002029 |
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| author | Enrico Caragliano Stefano Bonazza Giada Frascaroli Jiajia Tang Timothy K. Soh Kay Grünewald Jens B. Bosse Wolfram Brune |
| author_facet | Enrico Caragliano Stefano Bonazza Giada Frascaroli Jiajia Tang Timothy K. Soh Kay Grünewald Jens B. Bosse Wolfram Brune |
| author_sort | Enrico Caragliano |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-12-11T10:10:47Z |
| format | Article |
| id | doaj.art-19f814b0feb24c2395020321e8b28f80 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T10:10:47Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-19f814b0feb24c2395020321e8b28f802022-12-22T01:11:45ZengElsevierCell Reports2211-12472022-03-013810110469Human cytomegalovirus forms phase-separated compartments at viral genomes to facilitate viral replicationEnrico Caragliano0Stefano Bonazza1Giada Frascaroli2Jiajia Tang3Timothy K. Soh4Kay Grünewald5Jens B. Bosse6Wolfram Brune7Leibniz Institute for Experimental Virology (HPI), 20251 Hamburg, Germany; Centre for Structural Systems Biology, 22607 Hamburg, Germany; Institute of Virology, Hannover Medical School, 30625 Hannover, GermanyLeibniz Institute for Experimental Virology (HPI), 20251 Hamburg, GermanyLeibniz Institute for Experimental Virology (HPI), 20251 Hamburg, GermanyLeibniz Institute for Experimental Virology (HPI), 20251 Hamburg, GermanyLeibniz Institute for Experimental Virology (HPI), 20251 Hamburg, Germany; Centre for Structural Systems Biology, 22607 Hamburg, Germany; Institute of Virology, Hannover Medical School, 30625 Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, GermanyLeibniz Institute for Experimental Virology (HPI), 20251 Hamburg, Germany; Centre for Structural Systems Biology, 22607 Hamburg, Germany; Institute of Biochemistry and Molecular Biology, University of Hamburg, 20146 Hamburg, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, GermanyLeibniz Institute for Experimental Virology (HPI), 20251 Hamburg, Germany; Centre for Structural Systems Biology, 22607 Hamburg, Germany; Institute of Virology, Hannover Medical School, 30625 Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany; Corresponding authorLeibniz Institute for Experimental Virology (HPI), 20251 Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Hamburg, Germany; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124722002029liquid-liquid phase separationLLPShuman cytomegalovirushuman herpesvirus 5Herpesviridaereplication compartment |
| spellingShingle | Enrico Caragliano Stefano Bonazza Giada Frascaroli Jiajia Tang Timothy K. Soh Kay Grünewald Jens B. Bosse Wolfram Brune Human cytomegalovirus forms phase-separated compartments at viral genomes to facilitate viral replication Cell Reports liquid-liquid phase separation LLPS human cytomegalovirus human herpesvirus 5 Herpesviridae replication compartment |
| title | Human cytomegalovirus forms phase-separated compartments at viral genomes to facilitate viral replication |
| title_full | Human cytomegalovirus forms phase-separated compartments at viral genomes to facilitate viral replication |
| title_fullStr | Human cytomegalovirus forms phase-separated compartments at viral genomes to facilitate viral replication |
| title_full_unstemmed | Human cytomegalovirus forms phase-separated compartments at viral genomes to facilitate viral replication |
| title_short | Human cytomegalovirus forms phase-separated compartments at viral genomes to facilitate viral replication |
| title_sort | human cytomegalovirus forms phase separated compartments at viral genomes to facilitate viral replication |
| topic | liquid-liquid phase separation LLPS human cytomegalovirus human herpesvirus 5 Herpesviridae replication compartment |
| url | http://www.sciencedirect.com/science/article/pii/S2211124722002029 |
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