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.
Their 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 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, they showed that the structure is also present in SARS-CoV-2-induced DMVs.
The authors "surmise" 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.
Although the exact mode of function of this molecular pore remains to be elucidated, it...may offer a general coronavirus-specific drug target."
Wolff, G., et al, Department of Cell and Chemical Biology, Leiden University Medical Center
Wolff, G., et al. (2020) A molecular pore spans the double membrane of the coronavirus replication organelle. Science. doi.org/10.1126/science.abd3629.