RNA viruses, including the SARS-coronavirus, modify the membranes of host cells to form viral replication complexes. Coronaviruses induce double-membrane vesicles (DMVs), but the role of these structures in replication and viral fitness remain unclear.
Previous studies have established a role for coronavirus nonstructural proteins nsp3, nsp4 and nsp6 in DMV formation. Using murine hepatitis virus as a model coronavirus, Mark Denison, M.D., and colleagues tested how mutations across the nsp4 protein affect DMV formation and viral replication and fitness.
They found that mutations that affected DMV morphology but not nsp4 glycosylation (the addition of carbohydrate groups to nsp4) did not affect viral fitness, while viruses lacking nsp4 glycosylation exhibited both DMV alterations and a loss of fitness.
The results, reported in the Feb. 15 Journal of Virology, support a critical role for nsp4 in DMV formation and virus fitness. Defining the role of membrane modifications like DMVs is essential for understanding virus replication and developing novel approaches for inhibition of coronavirus infection.
This research was supported by the National Institutes of Health (grants AI050083, HL697659).
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