The Spatiotemporal Organization, Dynamics, and Function of Virus Replication Centers during Murine Polyomavirus Infection

Small DNA viruses require both host DNA replication and repair factors for their replication. The host cell replication factors are often recruited by the virus to subnuclear domains referred to as viral replication centers (VRCs). Several factors have been immunolocalized to VRCs using fluorescence microscopy, but little else is known about VRC spatiotemporal organization or dynamics. We investigated the organization and function of VRCs during murine polyomavirus (MuPyV) infection using 3D structured illumination microscopy (3D-SIM). We immunolocalized viral and cellular VRC components to spatially distinct VRC subdomains through which viral DNA (vDNA) trafficked sequentially post-synthesis, suggesting these VRC subdomains have distinct functional roles in vDNA processing. We also observed the disruption of VRC organization and function during mutant MuPyV infections or inhibition of DNA synthesis. These results reveal a dynamic organization of VRC components that coordinates MuPyV replication during infection

 

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