SARS-CoV-2 RNA May Move Through Tiny Pore in Peculiar Intracellular Double-Membraned Replication Vesicles into Cytosol for Packaging into Complete, Infectious Virus; Pore in Double-Membraned Vesicle Revealed by Electron Tomography

By visualizing coronavirus replication in an infected host cell, researchers may have answered a long-standing question about how newly synthesized coronavirus components are able to be incorporated into fully infectious viruses. The scientists’ work uncovers a coronavirus-specific structure in cells that may be a target for much-needed antiviral strategies against this family of viruses. Coronaviruses replicate their large genomes in the host cell's cytoplasm. They do this by transforming host cell membranes into peculiar double-membrane vesicles (DMVs). Newly made viral RNA needs to be exported from these DMVs to the cytosol to be packaged into complete, infectious forms of the virus. To date, however, no openings to the cytosol have been detected in the DMV replication compartments. Here, seeking to understand how viral RNA is exported from sealed DMVs, Georg Wolff (photo), PhD Candidate, Department of Cell and Chemical Biology, Section Electron Microscopy, Leiden University Medical Center, Leiden, The Netherlands, and colleagues used electron tomography to visualize the middle stage of infection of a cell by mouse hepatitis coronavirus, used instead of SARS-CoV-2 due to biosafety constraints for in situ cryo-electron microscopy studies. They identified a coronavirus-specific crown-shaped structure--a molecular pore spanning the two DMV membranes--that likely plays a role during RNA release from the compartment. In further work using pre-fixed samples of SARS-CoV-2-infected cells, the researchers showed that the structure is also present in SARS-CoV-2-induced DMVs. The authors "surmise" that this structure may be a generic complex with a pivotal role in the coronavirus replication cycle, facilitating the export of newly synthesized viral RNA from the DMVs to the cytosol.
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