Robert Kalejta - An Evolutionary Chess Match
A Virus is Smarter than You
Unlike a common cold where you’re sick for a few days and then you clear the virus and return to health, some viruses go dormant and hide within the cell. A virus that’s good at hiding can persist for the life of the host. And that takes some know-how on the part of the virus.
“We work on human cytomegalovirus,” said Rob Kalejta, PhD, associate professor of molecular virology and oncology at the University of Wisconsin School of Medicine and Public Health. “It’s a herpes virus, similar in some respect to the herpes simplex virus that would give you a cold sore. Our work is about understanding how the virus replicates and persists with the host. Just as the virus has learned how to use that defense against the cell, we’re trying to relearn how to use that defense against the virus. Evolution will do that in a couple million years, but we’re trying to speed up the process.”
What Kalejta and his lab are after is learning how the virus controls its own gene expression. During the two common types of infection, lytic and latent, a virus does two very different things depending on interactions with the environment.
During a latent phase of an infection, viruses are repressed and remain dormant within the host and cease creating more viral DNA. For human cytomegalovisus (HCMV), that means being repressed by cellular proteins. But HCMV actually uses those proteins to hide from the immune system. What’s more, the virus knows how to deactivate those proteins.
“When the virus wants to replicate or amplify the number of viruses that are present, it can inactivate those cellular mechanisms,” said Kalejta. “We’re interested in finding ways to modulate how the virus controls this defense. “We want to learn how to turn this cellular defense off so the virus can’t establish latency where it hides from the immune system, or if the virus is activley replicating, to turn the defense back on to inhibit virus multiplication.”
“I’ve been working on HCMV since my postdoctoral work at Princeton, almost 17 years now,” he said. “I have a love-hate relationship with it; I hate what it does to people but it’s extremely smart and it teaches us a lot about how cells work.”
That’s the other interesting thing with viruses, noted Kalejta. Because viruses must replicate inside cells, if they don’t know what’s going on in a cell, they aren’t going to survive. He suggests that any topic you’re interested in, whether it’s cancer, cardiovascular disease, immunology or anything involving a cellular process, you might benefit by asking a virus.
“Viruses are smarter than us. They’ve been studying the cell for millions of years. By studying viruses, we can learn not only about the virus, but also about basic cellular processes that might be applicable to other areas of research,” he said.
Progress, One ‘Basic’ Building Block at a Time
The Kalejta lab keeps making discoveries and continues moving the science forward. They hope the information they’re generating about the virus through basic research can one day be applied in clinical research. But it’s slow going, building the case against HCMV block by molecular block.
“It’s very technically challenging and you have to repeat research multiple times before you can believe it. Patience isn’t one of my greatest traits, but it’s certainly something you have to have as a researcher,” said Kalejta. “The way I look at it is that the basic science work that we do is like teaching a child the alphabet or how to read. That won’t make them a novelist, but if they don’t know how to do that, then they will never develop the skills to write the great American novel. We’re building the skills that others can use to be directly clinically related.”
A great motivation for Kalejta is the many scientific discoveries that were based on research from 20-30 years ago that had no immediate practical application. Like in the UW’s McArdle Laboratory: Howard M. Temin discovered reverse transcriptase. His discovery of how tumor viruses act on the genetic material of the cell through reverse transcription won the Nobel Prize for 1975, and now it’s a key enzyme in the fight against the HIV and AIDS epidemic.
“When you do an experiment and get the answer you expect, you don’t learn anything. The exciting times are when you get a completely different answer,” he said. “Those are confusing times, times that are difficult to convince others in the field, times when it can be difficult to get the resources to pursue the work, but those are the exciting times.”