Human cytomegalovirus forms phase-separated compartments at viral genomes to facilitate viral replication

Cell Rep. 2022 Mar 8;38(10):110469. doi: 10.1016/j.celrep.2022.110469.


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.

Keywords: Herpesviridae; LLPS; human cytomegalovirus; human herpesvirus 5; liquid-liquid phase separation; live-cell imaging; membrane-less organelle; molecular virology; phase transition; replication compartment; viral replication.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Nucleus / metabolism
  • Cytomegalovirus* / genetics
  • Cytomegalovirus* / metabolism
  • DNA, Viral / genetics
  • DNA, Viral / metabolism
  • Genome, Viral
  • Humans
  • Viral Proteins* / metabolism
  • Virus Replication


  • DNA, Viral
  • Viral Proteins