Researchers from several European institutions have discovered that virus infection causes a reconfiguration of cellular proteins involved in RNA metabolism. These results could be applied in the design of antiviral agents using as targets cell proteins that are dispensable for the cells but necessary for the virus.
A European team led by the University of Oxford, in collaboration with researchers from the Autonomous University of Madrid, has discovered that Sindbis virus (SINV) infection causes a global reconfiguration of proteins that bind to RNA in the cell.
This work, which has been based on a novel technique called RNA interactome capture, details that the virus activates and deactivates more than two hundred proteins involved in the metabolism of cellular RNA and redirects them to facilitate viral replication. The results have been published in the journal Molecular Cell.
As part of the work, the researchers observed that the proteins activated by the virus change their location in the cell and are recruited to the cell compartments where the virus replicates.
According to first author Manuel García Moreno, “the virus produces huge amounts of RNA as a result of its replication, and its accumulation has the effect of a spider web, trapping the proteins that the virus needs in the places where the virus replicates.”
‘Spider web’ effect
“This ‘spider web’ effect is complemented with the degradation of cellular RNA to eliminate competitors in the capture of these proteins,” García Moreno adds.
The authors show the importance of changes in the amount of cellular and viral RNA molecules through the genetic elimination of the protein responsible for destroying RNA, XRN1.
Alfredo Castelló, director of the work, explains that “when XRN1 is eliminated the virus cannot replicate. It is as if we took from the virus the key to open the cell and take its resources.”
“These results may be used to design new antiviral agents that inhibit the cellular proteins needed by the virus. In addition – adds Castelló -, it is likely that some of these proteins are necessary for other viruses, which would open the possibility of developing broad-spectrum antivirus. ”