04/07/2017

Giant Viruses Beefed Up On Host Genomes

12:02 minutes

Giant viruses grow by acquiring DNA from other organisms. Credit: Carla Schaffer/AAAS

Giant viruses can reach sizes larger than some bacteria and contain genomes that can encode hundreds of proteins. These outsized particles straddle the line between viruses and cellular organisms and their origin is up for debate – did they evolve from smaller viruses or an unknown ancestral organism.  A group of scientists discovered four new species of giant virus called Klosneuviruses in a wastewater treatment plant in Austria and analyzed the genome to come up with a hypothesis that these giant viruses evolved by picking up DNA from other organisms. Microbiologist Frederik Schulz, an author on the study, discusses what this information can tell us about viruses big and small.

[This giant virus was found frozen in Siberian permafrost.]


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Segment Guests

Frederik Schulz

Frederik Schulz is a Bioinformatics Postdoctoral Fellow in the Department of Energy Joint Genome Institute at Lawrence Berkeley National Laboratory in Walnut Creek, California.

Segment Transcript

IRA FLATOW: This is Science Friday. I’m Ira Flatow.

Viruses are the sources of many diseases. That’s actually their only purpose, to infect and replicate. But even though they’re the cause of many illnesses, when it comes down to it, they’re pretty simple and they’re pretty small, just a coating surrounding genetic material.

But there are a class of giant viruses. They contain 100 times more genes than the normal virus. They’re so big, some of them can almost reach the same size as bacteria. And there’s a debate surrounding how exactly these viruses evolved. Did they come from some unknown cellular ancestor? Or are they beefed up versions of smaller viruses?

The genome of giant viruses found in a wastewater treatment plant in Austria has now been studied to help unravel this mystery. The research was published this week in the journal, Science.

Frederik Schultz is an author on that study. He’s also a bioinformatics post-doctoral fellow at the Department of Energy’s Joint Genome Institute, part of the Lawrence Berkeley National Lab in Walnut Creek, California. Welcome to Science Friday.

FREDERIK SCHULTZ: Hi, it’s a great pleasure to be on the program.

IRA FLATOW: Well, it’s very nice to have you. Thank you. So I said that viruses are made of two things. There’s a protein shell and genetic material. How did giant viruses beef up, then, to get so big?

FREDERIK SCHULTZ: Yes, that’s a very intriguing question. And I think many researchers were thinking about this in the last one or two decades since giant viruses were first discovered. And it was very unexpected. As you said already, virus is usually very streamlined. They really have genes only to do necessary things to do effective infection of the host and replicate inside of the host. And you would not expect to find that many genes in a virus genome. So there are different ideas how giant viruses become so big.

IRA FLATOW: Now, there’s one idea that these giant viruses evolved into what they’re calling a fourth domain, that maybe there’s a new branch on the tree of life. So tell us a little bit about that idea and what the other ideas might be.

FREDERIK SCHULTZ: Sure. So the question is, if there is a fourth domain– and there were ideas that giant viruses originated from cellular organisms as it’s adjusting, so unlikely to accumulate so many genes, which are usually found in cellular organisms. And so the more likely approach would have been that this virus indeed came from cellular organisms, that they were from a cellular organism. And this cellular organism could have been part of [INAUDIBLE] fourth domain of life, which we did not sample yet, which we did not discover yet, and which eventually, is already extinct.

And yes, so researchers thought, well, this could be the explanation that we find these cellular genes in giant viruses. So we postulated these giant viruses might be the remnants, or they might just represent such a fourth domain of life.

IRA FLATOW: Is that what you think?

FREDERIK SCHULTZ: I think when we first discovered this new group of viruses and we saw that they have such a much more comprehensive complement of these genes than are typically found in cellular organisms, really wanted to prove, they really wanted to show that they come from this cellular ancestor, because that just sounds supercool. And they really like this idea.

And I heard talks from Chantal Abergel, who is at the university in Marseilles and who did a lot of amazing work with giant viruses in the last 10, 15 years. And yeah, I really admired this idea. And I thought, now we have some kind of chance to really prove this.

And we are not from the giant virus field, so we came into this study rather unbiased. And in the end, I think what we found just didn’t give us any support for this fourth domain of life hypothesis.

IRA FLATOW: And so you analyzed the genetic material of four new species of giant viruses. And what’s the general name we give to these viruses?

FREDERIK SCHULTZ: So we gave them the name Klosneuvirus. So as you already said, they were initially discovered in a sample from a wastewater treatment plant in Klosterneuburg, Austria. And based on the genetic material we found in there, we then made use of this genes to screen through thousands of environmental metagenomic data sets. And we found related viruses in, I think, around 50 of these data sets. And three of them had these viral genomes in very good quality inside. And those we took for a comparative analysis. And it seems that they’re all the closest relatives to Klosneuvirus. So based on that, we could define this new group of giant viruses, which were then called Klosneuviruses, as they are based on the site where the first one was discovered.

IRA FLATOW: So you think that these giant viruses may have grown in size as they evolved, as they went along, picking up other remnants?

FREDERIK SCHULTZ: So this is one factor, picking up other genes from, as you said, foreign genetic material, which can come from the host. So we should keep in mind, these giant viruses, at least the ones we know today, they infect protists. So these are like unicell eukaryotes, like very small partially rather primitive cells. And they thrive inside the cells. In protists, they take up a lot of other organisms in the surroundings. They take up bacteria, fungi, other protists. They take up viruses, and they digest all this. So a lot of genetic material is set free in these protists. And giant viruses are also in there. And giant viruses, they can persist in this proto cytoplasm.

And one idea was that due to all of this big pool of DNA, it’s more likely to take up genes. And there seemed to be some mechanisms which allowed integration of these genes into the giant virus genome. But actually, it’s not that simple. It’s just one thing to acquire a new gene. But giant viruses, they also extensively duplicate these genes. So they start to generate multiple copies of this gene in their genome. And they evolve these genes. And some get thrown out again, and others, maybe work with additional important beneficial functions in the host interaction.

IRA FLATOW: Wow, so they suck up all this genetic material. They grow giant. And they spit out what they don’t need to keep going.

FREDERIK SCHULTZ: So that’s the idea.

IRA FLATOW: That’s the idea. But you actually haven’t found the virus itself, have you? You found signs and remnants of the virus? Do you have to go fishing now back to this that cesspool the waste treatment place and find the real virus?

FREDERIK SCHULTZ: Sure, I think that would be the best thing to do. And I think it’s being done right now by a collaborator at the University of Vienna. But it’s not so easy to do it. So the thing is, as I said, these giant virus, they’re usually found in protists. And previous giant viruses, they have been isolated usually in co-cultivation with protists. So often, these native hosts of the giant viruses are not accessible for isolation. Maybe we don’t have the right conditions to get them. So it’s very tricky to isolate them.

And also, the giant viruses often are very allergic to the hosts. So they might just destroy the host population in a short period of time. So yes, usually, they take a sample from the environment, and they destroy all [INAUDIBLE] material in there, something like using strong heat or so. And the viruses, they survive. And then they take the sample and they put it on a culture of like, let’s say, amoebae. And some giant viruses are able to infect this amoebae. And that’s how they isolate these giant viruses.

But it seems that for Klosneuvirus, this doesn’t work in that way. So because they’ve never been isolated before, based on our environmental survey, it seems that they are fairly abundant. So as I said, we found them in 50 samples all over the world.

IRA FLATOW: Yeah. A lot of people say, why do you care about a giant virus? I mean, apart that it’s giant and people like giant things, why should you– what’s so interesting about it to you?

FREDERIK SCHULTZ: I think to me it was most exciting to see how close viruses can actually become to cellular organisms. And as you already said, I think the most striking part– I still remember during my master studies at the University of Vienna, I had a course where I had to present a study about mimivirus. And I was so fascinated by it, to see that these kind of viruses can exist. And so I was really struck by seeing what viruses are capable of, and that they can come so close to cellular life with their genetic equipment. So that, I think, it makes it really exciting to see. And from an evolutionary perspective, it’s really a great thing to study giant viruses.

IRA FLATOW: You know, as you say, we only discovered them about 10 years or so ago. But we all thought that viruses are very small. Could there now be many more giant viruses out there we don’t know about because we never looked for them because we thought they were so small?

FREDERIK SCHULTZ: I think one problem was, in the past, that when they tried to isolate viruses, they usually used penetration, so they take all particles which are fairly small, which pass through the filter. And that’s like the virus wrecked them. And this has been studied. And giant viruses, they won’t pass the filter because of the particle size. So they I think in many previous studies, they got missed. And I think also the first discovery of giant viruses was not so clear that they were indeed viruses. And it was expected that these are bacteria because of the size. And only later, when they used something like electron microscopy, they saw that this looked like viruses.

And I think giant viruses are out there. That’s for sure that there are many, many more. And I mean, in the course of this study, I saw, I think, around 6,000 or 7,000 metagenomes from environmental samples all over the world. And I saw that there are really many, many giant viruses. And as I said, the problem is the cultivation, that the ones we know, usually, they could be cultivated with the host. But I think the majority are not so easily accessible for cultivation. And these [INAUDIBLE] studies are the best, I guess.

IRA FLATOW: What is the evolutionary advantage of being a bigger virus over a smaller virus?

FREDERIK SCHULTZ: It’s a great question. And we thought a lot about it because this new crop of giant viruses, they have almost a complete set of translation system genes. So there’s this kind of thing that we would not really not expect in a virus. And it’s one of the criteria we thought viruses definitely don’t do a translation. And we don’t have any evidence that Klosneuvirus or the newly discovered viruses do it. But it might be imaginable that under certain conditions in the environment– for example, starvation of the host population, where the host metabolism gets slowed down– that in that case, this giant virus with such a genetic complement could take over the translation inside of the host cell. So they could eventually use the ribosome of the host and use their own genes, selective viral proteins to build up additional of viral proteins. So they could keep up replicating while the host slows down.

Alternatively, there was the idea that defense strategy, which we observed in eukaryotic cells, as well as in bacteria and infection by viruses, that they shut down protein biosynthesis just to avoid the further propagation of the virus. And one conceivable scenario could be that Klosneuvirus, for example, in that case, starts using its own proteins to build up additional proteins inside of the host.

IRA FLATOW: Fascinating, fascinating.

FREDERIK SCHULTZ: So yeah, these are really exciting questions, I think. But yeah, we really would need to isolate Klosneuvirus first together with its host to follow this up.

IRA FLATOW: I hope you have a very successful fishing expedition out there to find the virus. Thank you very much. Frederik Schultz is bioinformatics post-doctoral fellow at Lawrence Berkeley National Lab at the Department of Energy Joint Genome Institute.

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