A new study published in the open-access journal PLoS Pathogens has found that replication of coronaviruses – such as SARS – depends on two factors within the early secretory pathway.
As the cause of several respiratory and enteric (referring to the intestines) infections in both humans and animals, coronaviruses have been a recent focus of pathology research. The infection cycle of this class of viruses, as with all viruses, highly depends on cellular factors related to the host. After making its way into cells, coronaviruses begin systematic RNA replication in factory-like complexes that are linked to newly induced, double membrane vesicles. Researchers have not yet revealed the cellular pathways used by these plus-strand RNA viruses in creating these “factories.”
A team of Dutch researchers, led by Cornelis A. M. de Haan, has demonstrated that the drug brefeldin A inhibits RNA replication of mouse hepatitis coronavirus (MHV). It achieves this by interfering with the central station of the cell’s secretory pathway – called the Golgi complex. The authors were able to show consistent depletion of both the cellular target of brefeldin A and two factors that negatively affect infection the coronavirus’s infection: one factor called GBF1 and a second downstream called ARF1.
“An intimate association exists between the early secretory pathway and MHV replication,” write the researchers. Though GBF1 and ARF1 are not involved in forming the viral replication factories, the researchers suggest that the two factors affect their maturation or functioning. Their research specifically dealt with the mouse hepatitis coronavirus, and they call for further researcher studying the impact of GBF1 and ARF1 in the replication of other coronaviruses.
Mouse Hepatitis Coronavirus RNA Replication Depends on GBF1-Mediated ARF1 Activation
Verheije MH, Raaben M, Mari M, te Lintelo EG, Reggiori F, et al.
PLoS Pathogens (2008). 4(6):e1000088.
doi:10.1371/journal.ppat.1000088
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Written by: Peter M Crosta