Simulation shows how, where virus invades healthy cells

Researchers from the Penn State College of Medicine and the University of Pittsburgh School of Medicine have developed a new way of observing a virus’s shape using an experiment using a simulation of the interaction between virus and cell.

Susan Hafenstein, assistant professor at Penn State College of Medicine and lead researcher, hypothesized that only the part of a virus that interacted with receptors from a healthy cell would change shape. Using artificial membranes, called nanodiscs, the team inserted human cell receptors protein molecules that let outside signals into the nanodics.

"This particular receptor has a long tail that it buries into the cell membrane," said Hafenstein. "In our experiment, it buried its tail into the nanodisc, giving us a mock membrane displaying the appropriate receptor to bind to the virus."

Then adding the virus protein shell to the receptor membrane, the team was able to observe the change in the virus shape that occurred when it met the receptor. Using images from a cryo-electron microscopy, the team found that the virus only changed shape at the site of the connection with the receptors.

"Our work shows that a pore opens up only at that one point of interaction with the host cell," Hafenstein said. "And that's what's going to set up the capsid to release the genetic material into the cell. We think we have captured the first physiologically accurate virus capsid prepared to enter the host. All the ones that we had studied previously showed changes taking place all over the capsid."

By understanding the virus life cycle, Hafenstein hopes this simulation will lead the path to developing more direct anti-viral drugs.