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Interviewer: There's a war going on around us and most of us don't even know it. Dr. Nels Dr. Elde, assistant professor of human genetics is investigating the evolutionary arms race between viruses and ourselves. Dr. Dr. Elde you describe a so-called arms race between pathogens and humans, what do you mean by that?

Dr. Elde: One of the ways we think about this arms race is actually to do with a literary reference, and this is what's known as the red queen hypothesis. So this comes from Lewis Carroll's book, Through the Looking Glass, and the character the red queen who's talking to Alice. And she says, "It takes all the running you can do to just stay in the same place." We've kind of co-opted that idea for host-pathogen evolution. So the idea of an arms race at the molecular level is that we go in these back and forth counter adaptations where viruses and other bugs are having a negative impact on our health or fitness which leads to whether or not we're able to reproduce, and who is able to reproduce? On the other hand, when our populations are able to defeat a bug, this is another leg of the arms race. You can imagine this as just playing out again and again as evolution unfolds.

Interviewer: Every year we need a new vaccine for the different strains of flu that are circulating among us, is that an example of this race?

Dr. Elde: Yeah Interviewer, that is a great example of the arms race. Every year we come up with a vaccine, that is hopefully beneficial for knocking out influenza. Then what happens is that its only useful for so long because in this arms race scenario the influenza virus return with genetic variation that can defeat that vaccine.

Interviewer: Yeah, so how do they do it? What is there secret?

Dr. Elde: So these vaccines are designed to recognize certain shapes, basically, on the surface of the virus. If we're able to effectively recognize those shapes it'll alert our immune system to come in and destroy the viruses. So what the viruses do is then through mutations and selection of their genes, change their shapes and then they become virtually invisible to our vaccines.

Interviewer: So how do you study these host-pathogen interactions in the lab?

Dr. Elde: In particular, one of the viruses we study is called vaccinio virus. It's the model pox virus. The pox viruses are most famous medically for small pox. One of the ways it was eradicated was through vaccination using a highly related but much more safe virus called vaccinia. And so what we do is take this relatively safe virus into the laboratory, present it with puzzles or challenges. For example, we give it cells if its not good at replicating. And then given all the advances in genome sequences technology, what we can do is sequence the genomes of the viruses before and after we present them with these immunity puzzles. And then ask what's different about the virus at the end...

Interviewer: Oh cool.

Dr. Elde: ...of the experiment.

Interviewer: Yeah.

Dr. Elde: Yeah, its pretty fun experiments. Of course, you have to be careful, we are dealing with viruses.

Interviewer: Yeah.

Dr. Elde: And so, one of the very cool findings from one of our initial studies of the vaccinio virus that really surprised us. Was that virus was adapting not only by, so called point mutation, where you exchange only one letter of DNA, so to speak, but these viruses were becoming, the genomes were becoming larger right in front of us. So even over the course of a few infections, the virus, the genome was increasingly in size up to 10-20%. It's really striking.

Interviewer: What does it mean for a genome to expand.

Dr. Elde: What I mean by this is if we just look at the size of a genome, for example, and for these pox viruses like vaccinia and smallpox there are about 200 kilo bases. This is 200,000 DNA letters in a row. What we found was that they're getting more letters. They were going from 200,000 letters to up to 220,000 letters. It wasn't just that you were adding, a gobbledygook of 20,000 letters, you were adding the same repetitive letters of about 300 in a row of a certain gene.
And it turns out this gene is actually an important inhibitor of one of our immune response genes. What we saw was that for this specific gene, it went from one copy, to as many as 20 copies, very quickly. Having 20 copies meant that the virus was much more able to defeat our immune response versus if it only had one copy. What was really- a second surprise was that once this virus had 20 copies of this gene, it was actually 20 times more likely to come up with a new single letter change or a point mutation, that in of itself could defeat the immune system.

Interviewer: So not only is it defending itself better but it is also driving it's own evolution.

Dr. Elde: Exactly.

Interviewer: That's so cool.

Dr. Elde: It's a two for one. It's cool but its also kind of scary. Right?

Interviewer: Yeah, right.

Dr. Elde: These things can really, and this is again sort of this idea of an arms race.

Interviewer: Yeah.

Dr. Elde: And its sort of any mechanism that can aid the virus in its replication will very quickly be selected for. The imagery we've been using to name this hypothesis is called the accordion model of virus evolution. The idea is that the virus expands as an accordion might, as a musician is playing part of a note, and then in this expanded form, you sample all of these extra copies for changes. If you hit on one that works then the accordion can contract the second part, it's like a musician playing the experiment, right?

Interviewer: Yes

Dr. Elde: But here the virus is playing evolutionary process and changing in ways that benefit its replication.

Interviewer: So, how can we use information like that to help combat these viruses?

Dr. Elde: We always want to look at what we see what we observe in the laboratory and ask, does this apply in the wild? There's this really interesting story with a pox virus that infects rabbits. It was purpose, the virus was called myxoma, it was purposefully released in Australia back in the 1950s as a biological control agent. The idea was that some of the settlers in Australia had brought rabbits from Europe. The rabbits had gone crazy and now billions of rabbits and you have a problem. One of the proposed solutions was to release a virus that could kill the rabbits. So this was myxoma virus.
So, there's this really interesting historical record where people save the virus years after it was released in the rabbits. What we believe, what we done is look at the genomic changes and we see hints of these gene duplication, or almost accordion-like dynamics. We think this could happen in the wild as viruses are exploring new hosts. What we're trying to do with this is trying to understand at a basic level, how these viruses operate, how they adapt, how they evolve. If we're in position to have that information before that happens, we might be in a much better spot to stop them before they get out of control as new epidemics or pandemics.

Announcer: Interesting, informative, and all in the name of better health. This is the Scope ÈËÆÞÖгöÊÓƵ Sciences Radio.