The vaccinia virus has a problem: it is a giant among viruses and needs a special strategy in order to infiltrate a cell and reproduce. Professor Ari Helenius and Postdoc Jason Mercer from ETH Zurichs Institute for Biochemistry have now discovered what this strategy is. In the process, they stumbled upon new and surprising findings.
The invasion strategy
In order to infiltrate a cell, the vaccinia virus exploits the cellular waste disposal mechanism. When a cell dies, other cells in the vicinity ingest the remains, without needing waste disposal experts such as macrophages. The cells recognize the waste via a special molecule, phosphatidylserine, which sits on the inner surface of the double membrane of cells. This special molecule is pushed out as soon as the cell dies and is broken into parts. The vaccinia virus itself also car-ries this official waste tag on its surface. The substance accumulates on the shell of vaccinia viruses, Jason Mercer explained. The pathogen disguises itself as waste material and tricks cells into digesting it, just as they normally would with the remains of dead cells. As the immune response is simultaneously sup-pressed, the virus can be ingested as waste without being noticed.
The uptake into the cell itself is via macropinocytosis. The ETH Zurich researchers have demonstrated that the vaccinia virus moves along actin-rich filamentous extensions towards the cell. As soon as they impinge upon the cell membrane, an evagination forms, a bleb. The virus itself is the trigger for the formation of the evagination. Using a messenger substance to knock on the door, the virus triggers a signaling chain reaction inside the cell so that the bleb forms, catches the virus and smuggles it into the cell.
Proteins as unsuspecting allies
The viruses are the Trojan horses that want to enter Troy; the Trojans are the many proteins that transmit the signals and open the city gate
|Contact: Jason Mercer|
ETH Zurich/Swiss Federal Institute of Technology