A Model of Epstein— Barr Virus
A new simulation mimics the virus’s infection cycle on the tonsils, shedding some light on how the infection spreads
During our lives, most of us will come in contact with the Epstein-Barr virus, commonly known as that bane of teenagers, infectious mononucleosis. Now, a new simulation mimics the virus’s infection cycle on the tonsils, shedding some light on how the infection spreads.
“The actual biology is so complicated,” says David Thorley-Lawson, PhD, professor of pathology at Tufts University who co-leads the project with Karen Duca, PhD, a biophysicist formerly at the Virginia Bioinformatics Institute (now at Kwame Nkrumah University, Ghana). “But what we got out of the simulation looks remarkably like a real infection.” They and others developed the Pathogen Simulation (PathSim) model published in the October 2007 issue of PLoS Pathogens.
The potential benefits of modeling infection seem endless. Scientists can raise the viral load in ways that would be un- ethical in humans; and insight into the dynamics of infection could lead to novel therapies. But the question remains: Do the models truly replicate how infection spreads in the body?
Until now, most computer modeling only reproduced general properties of the immune system, or involved the use of differential equations to provide more specific insights, such as with some HIV models. Using a well-studied virus like Epstein-Barr as a guide, Thorley-Lawson and colleagues believed they could create a model that rivaled the sophistication of HIV models while remaining comprehensible to nonspecialists.
“One of the main goals was to have models that biologists could look at and say, ‘Oh, I get that,’” says Thorley-Lawson. To accomplish this goal, the researchers created a ring of tonsils—the point of attack for Epstein-Barr virus—on a virtual grid.
During the simulation, the virus infected cells at about the same rate it does in a person. “This suggests we’re not missing huge parts of the biology,” says Michael Shapiro, PhD, co-lead author and lecturer in pathology at Tufts.
Already, the model has helped explain a clinical puzzle. Several years ago, Thorley-Lawson and his team found that when Epstein-Barr causes infection in vivo, only 0.5 to 1.0 percent of the host’s B cells—key sentinels of the immune system—replicate the virus. At the time, the researchers didn’t know why that replication rate was so low.
When an almost identical proportion of the model’s B cells were active at the same stage in PathSim, Thorley-Lawson and his colleagues increased the number of B cells replicating the virtual virus to see what would happen. This tinkering “killed” the virus’s host by overwhelming it with infected B cells. According to PathSim, the virus has honed in on the speediest possible replication rate while still keeping its host alive—thus ensuring its further spread.
“This is a very nice first step,” says Alan Perelson, PhD, a biophysicist at Los Alamos National Laboratory. He acknowledges that as PathSim becomes more complex, it will rely on more biological assumptions. Still, he says, “The model looks like it’s driving some new experimentation.”