Honey Bee Viruses with Dr. Michelle Flenniken (S6, E48)

S6, E48 - Honey Bee Viruses with Dr. Michelle Flenniken

Amy Seiber: Hi. My name is Amy Seiber. I work at Foxhound Bee Company in Birmingham, Alabama. I personally have five hives. Welcome to  Beekeeping Today  Podcast.

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Jeff Ott: Welcome to  Beekeeping Today Podcast, presented by Betterbee, your source for beekeeping news, information, and entertainment. I'm Jeff Ott.

Becky Masterman: I'm Becky Masterman.

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Hey, thank you, Amy Seiber, from Alabama for that great opening. I remember talking to you at the North American Honey Bee Expo way back in January. It's fantastic. I love these listener openers.

Becky: One more state added to the map. I have a question for you about these states, Jeff.

Jeff: Yes.

Becky: If we get more people from Alabama like Amy, are you going to be able to shade in the state to represent the number of listener openers from each state? Is that a thing or should we just work on filling out the state map first?

Jeff: Geez, I hadn't thought of that, but we'll have to do something. Maybe we'll just add them to the list of people doing an opener for that state. We'll just leave the color the same.

Becky: Are you busy right now because it's swarm season? Is that why you're not taking on this little task?

Jeff: Is that why you're poking me right now? Yes. Swarm season is here. It is not fun because every time I see a swarm take off, it's-- Last year was horrible. This year I hope to do better. Last year my focus was somewhere else and not on my bees and they let me know it. I just had swarms left and right. I am committed to doing better, both in preventing swarms and trying to chase them down.

Becky: It's one of those things where swarms are a sign of-- that the environment is healthy, that they're strong enough to think that it's a great time to reproduce and divide the colony, but boy, oh, boy, it is also a reminder that we need to keep our eyes on those bees and make sure they have space and make sure that queen cells aren't started. What is it, a full-time job with just two colonies, probably?

Jeff: Yes, it really is. It can become that way. What do you recommend for a beekeeper who opens their hive on a spring inspection or late spring inspection, as we are now, and you see some swarm cells hanging off the bottom of the frames? What do you recommend? Do you let them swarm? Do you trim off those queen cells? What do you do?

Becky: First thing, I recommend that they panic. That's a really good step.

Jeff: I'm good at that.

Becky: Start by panicking.

Jeff: I'm good at that. Check.

Becky: Then it's a good time to phone a friend or a mentor if you don't have experience, but I wouldn't recommend handling those queen cells too quickly. You want to make sure that you're not actually maybe seeing emergency cells or supersedure cells. It makes sense to give yourself time to panic and then take a deep breath and make sure that what you're looking at is a swarm.

I say that with full confidence, but it's actually hard to tell sometimes. There are those signs, like extreme crowding, you could have a situation where you look in the brood nest and it's full of nectar because they have no place to store that incoming food, but the other thing that could happen is that your colony could have already swarmed and so those swarm cells that you're looking at could be the next queen in your colony. Whatever you do, don't make the first step taking those cells down, because you need to evaluate the situation.

Jeff: Maybe lower that brood box down gently and evaluate your situation before you get in there with the hive tool and start cutting out those queen cells.

Becky: Yes. You panic away from the colony. No panic queen cell culling allowed because you could get yourself into a bit of a bind.

Jeff: That is really good advice because I think every beekeeper's gone through and cut out queen cells and then sat back later in the evening and thought, "Well, maybe they needed those queen cells," and then three weeks later find that you have a queenless colony there.

Becky: That's a whole other problem you get to have if you don't have a queen. One problem at a time.

Jeff: That's right. That's right. Hey, today's guest is Dr. Michelle Flenniken of Montana State University. I am looking forward to this conversation because her specialty is the viruses. For me, the whole concept of the honey bee immune response and immune system is fascinating. I want to learn more about this, so I'm hoping she can shed some light on that for us.

Becky: Absolutely. Looking forward to it.

Jeff: All right, well, let's get to our conversation with Doctor Flenniken real quick, but first, a couple words from our sponsors.

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Jeff: Hey, everybody, welcome back. Sitting across the virtual  Beekeeping Today Podcast table is Dr. Michelle Flenniken from Montana State University. Michelle, welcome to the podcast.

Dr. Michelle Flenniken: Thank you. Excited to be here.

Becky: So glad you're here, Michelle. Thanks for taking the time to talk to us.

Jeff: Michelle, we've invited you here to talk a little bit about honey bee and pollinator immune systems and the work you're doing in that field, but before we get to that, can you tell us a little bit about yourself and how you got started in this area of bee study?

Michelle: Yes. As you mentioned, I'm a professor at Montana State University currently, and research in my lab is focused on honey bee immune responses and the viruses that infect them, the interaction between viruses and bees. How I got here is an interesting route anyway. I knew I always wanted to be a scientist. When I did my PhD, I worked with viruses as a nanotechnologist. We use viral capsids and viral-like capsids to deliver things like chemotherapeutic agents or imaging agents to targets like cancer cells, for example, because when you think about it, viruses are experts at targeting areas of the body where they infect or localize, and so my PhD focused on that.

I did that, actually, at Montana State, where I decided to come back to. I was a postdoctoral scientist at the University of California in San Francisco. There I worked in a primarily human health lab with Raul Andino and Joe DeRisi. My project initially was on human health. Raul Andino is an expert in polio virology, actually. UCSF is a primarily human health institute, but about a year into my postdoctoral research, I got in honey bees, especially at that time around 2008, where that was really the height of the initial description of colony collapse disorder.

I was just down the road from UC Davis and Dr. Eric Mussen, and also Christi Heintz, who was affiliated with Project Apis m., was really interested in getting other scientists, not just entomologists or experts in bees, interested in honey bee science. That's when Joe DeRisi and I and a graduate student, Charles Runckel, joined the honey bee research area. We first teamed up with commercial operations and examined viruses in those operations. Really that's where my honey bee virology study took off there at UCSF. Then I was lucky enough to bring that whole project with me to Montana State University.

Of course, Montana's a big beekeeping state, and they think they're happy to have a bee researcher here at MSU. UCSF was probably glad to see one go because, again, I mentioned [laughter] they were excited about human health there. While honey bee health contributes to human health, as we all appreciate, they're really focused on really human health.

Becky: I love that origin story. I did not know that about Christi recruiting you. That's pretty interesting and lucky us.

Jeff: I have to ask, what's a capsid?

Michelle: Oh, a capsid. Sorry. It's jargon for the shell around the virus. Viruses are really just nothing more than a protein shell that encloses their nucleic acid. Viruses can have genomes that are made of DNA or an RNA. If that's a little bit too much to take, depending on where you're listening to this, you can think of a virus as a little tiny little M&M. The candy shell would be their capsid or the protein, and the little chocolate center would be their nucleic acid or where their genome is stored.

Jeff: I have all sorts of visual jokes coming to mind, but I'll just let them all go for our listener's sake. That's really fascinating because there has been a lot of research and I guess the public became aware of it during the COVID days of all the research that's being done around viruses and at least have a layman's understanding of that research. It's fascinating and exciting to hear that some of this technology is already in play for our honey bees.

Michelle: The same tools that we used to study the viruses that infect humans are the same exact tools we used to detect viruses and quantify them in honey bees. In fact, my lab, initial days in the pandemic here in Bozeman, Montana, we moved our operation to the hospital, and we performed initial testing for SARS coronavirus 2, which is the causative agents of COVID-19, the pandemic. It was interesting to walk into the hospital, and people knew me around town as somebody who studies honey bees and gives talks like that, so they were surprised to see me in the diagnostics lab at our local hospital. I could quickly explain to them that the tools are the same.

Jeff: They weren't worried that our honey bees were getting COVID as well. Were they?

Michelle: No.

[laughs]

Jeff: Well, let's not start that rumor.

Michelle: No.

Becky: Michelle, can I ask you, when you switched from humans to honey bees, what was your thought of the state of our knowledge about honey bee viruses at that time?

Michelle: I would say there was really early papers by Ball and Bailey, and there was descriptive studies of looking at viruses under a transmission electron microscope or also associating really overt symptoms such as those greasy, shiny bees you see in the colony or bees with deformities in their wings, which can be caused by deformed wing virus, or also they can be caused by errors in development. If a mite bites the side of a bee in the larva or pupa phase, you can also get wing deformity.

Of course, deformed wing virus, if it infects the bees during larva development or pupa, early in development, it will cause wing deformities. It's important to know that deformed wing virus is very common, and we see it in adult bees at very high levels. If that virus infection occurs after the wings have already developed, then you'll have a virus that has deformed wing virus but won't have that characteristic wing deformity that we all look for.

I would say the state of honey bee viruses was really at the time, this would be around 2008, 2009, people knew there were viruses there, they had been described to the ability of that time, but they really hadn't been described using modern molecular techniques or the genomes hadn't been sequenced and matched with the antibodies that were available to detect them.

I think there was a lot of room for discovery, which as a young scientist that was really cool and exciting to me. Eric Mussen was really enthusiastic about bringing someone with that molecular expertise into honey bee research since he knew I would be coming at it from a different way. My background, as we've talked about already, isn't entomology. Sometimes, when you bring people from other disciplines in, you just think about it a little differently or question the things that I didn't have the background knowledge in.

Even today, the tools for studying honey bee viruses are much limited compared to those for studying human viruses. For example, things that we need to study honey bees are immortalized cell lines. Also, we can grow a cell in a dish. Dr. Mike Goblirsch, who may be a cool guest for you to have on, has one honey bee cell line, but for humans, we have hundreds, if not more than that, cell lines.

We can propagate viruses in the laboratory setting for humans. We have a harder time doing that for bees. A lot of the bee viruses are the same size and shape. They're a little tiny 30 nanometer size viral capsids. We already introduced that word today. They have little capsids. To give you a sense of that, about 5,000 of them would fit across the diameter of our human hair. Since many of them have the same size and shape, they co-purify. That makes studying them individually difficult for us. We still need more tools for honey bee virology.

Jeff: You used a term, I can't remember what it was, immortalized, or what was it?

Michelle: Those are cells that grow in a dish. I think most of us can maybe picture bacteria growing on a Petri dish or in a flask. We have that same technology in the laboratory to grow eukaryotic cells like human cells, epithelial cells. Those cells make up your skin. There's a really good book called  The Immortal Life of Henrietta Lacks that describes immortalized cells and what a key role they play.

In that particular book, they describe the use of HeLa cells. They're a type of cell line that was derived from a tumor of a woman named Henrietta Lacks. That cell line enabled the production of the polio vaccine, which really then, we all benefited from the polio vaccine. Without being able to produce a lot of poliovirus and inactivate it, we couldn't have the vaccine. This is what we call immortalized cell line. Having a cell line that you can infect with a virus is a very important tool for a virologist to either make vaccines, study that interaction. We have one honey bee cell line.

Becky: Is anybody trying to develop another one? I witnessed a lot of what Mike did at the University of Minnesota, and it was painful.

Michelle: Many people have tried and many people-- There aren't any. There was one described in South Africa. For me as a scientist who runs a lab that's composed of graduate students and undergrads and then myself, it would be a risky project to bank somebody's PhD on making a honey bee cell line. I think there's been side efforts, nothing's come of it. I would say it's not a concerted effort in my lab even though it's so important to have it because I can't really bank somebody's future scientific career on something that's very risky project.

I think a lot of people have worked on it. I couldn't name all the names, but it is a painful, slow process, and often it's just by trial and error. I forget what it said in that book about Henrietta Lacks' cells, but I think the doctors there were just taking a biopsy of every tumor and trying to grow it, and then finally, number 1,000 grew. That's a mundane science that is, so it's hard to ask somebody to do that. It's good that Mike Goblirsch is continuing to work on it.

Becky: He's at the USDA lab now. I think that when I'm thinking about it, we as a national group, I don't think beekeepers are putting that in their ask to the USDA that we'd like another cell line because that's a perfect thing for the USDA to do, especially when they have him on board. Not that he wants to do it again. I don't know. Anyway, that's interesting.

Jeff: Michelle, you mentioned that the virus capsid, the virus M&M, is about the same between the honey bee, and I assume that's all insects or most insects, and the human. Are viruses between humans and honey bees or other insects, are they basically the same thing?

Michelle: No. They're really different in terms of what makes up that protein or capsid or candy shell. Although they're the same size and shape, meaning they'll co-purify because we use filtration and centrifugation to purify these viruses, the outer coats are capsid of black queen cell virus, which is a common honey bee infecting virus, it has a completely different protein than deformed wing virus capsid protein.

Those capsid proteins assemble to make that shell around the virus. Again, if we want to go back to human viruses, the shell around SARS coronavirus 2 is completely different than those. That's completely different, not even like you want to think of the different colored M&Ms, but they would have different shapes and protrusions on the outside of those, roughly soccer ball- shaped icosahedral of viruses.

Jeff: Maybe for a beekeeper, they'd be the pollen grains of the same size, but they're completely looking in different shapes.

Michelle: Yes. Then pollen grains would just be huge compared to the viral capsids, but yes.

Jeff: Very good. Let's take a quick break and hear from a couple of our sponsors and we'll be right back.

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Becky: Welcome back, everybody. Michelle, could you break it down in really easy-to-understand, kind of like M&M terms for our listeners about the workings of the honey bee immune system?

Michelle: Right. Honey bees like you and I have an immune system. That immune system is what's activated when a bee is infected with a virus. Then the overall goal, if the immune system has a goal, is to tamp down the levels of infection so that the bee wins, the cell of the bee wins. We didn't talk about what else I do in addition to bee research here at Montana State but I also teach genetics and virology. Your listeners have to have a little bit of genetics 101 and virology 101 here to understand the bee immune system.

Viruses are obligate intracellular pathogens. That sounds like a mouthful at first, but it means that a virus needs the honey bee cell to replicate in. They can't replicate on a grain of pollen. They can't replicate on a flower. A virus needs to be inside a cell. The virus, we say co-opts the host cell, uses the host cell machinery to basically photocopy itself or make more, replicate itself inside this honey bee cell, or in the case of human viruses, the same thing goes on in our cells.

That virus is replicating in there. Sometimes then that creates a reaction to that virus or components. The viruses that infect bees, RNA genomes. When they're replicating or photocopying themselves in the cell, they produce double-stranded RNA. That's a molecule. It's the replicating genome of that virus. That's strange for a honey bee cell. That's recognized by host cell proteins. The honey bee has proteins that recognize double-stranded RNA, and one of them is called dicer. Dicer does what its name suggests, it chops up that RNA. If you chop up the RNA of a virus, you don't have a virus anymore. That process of the immune system is called RNA interference.

Again, something that sounds technical, but if you know that the viral genomes are RNA and this method is called RNA interference, basically, just stops the virus. In addition to that, honey bees have what we call a non-specific double-stranded RNA-triggered immune system. It's not sequence-specific. It's an area of particular interest in my lab. Again, it's RNA-triggered but different proteins are involved, and we're trying to figure out those mechanisms. Honey bees also have what we call just innate or canonical immune response pathways, which basically activate or turn on an expression of a lot of genes that might help tamp down that virus. Depending on the particular virus, that host response may vary.

Becky: Thank you. That was more of a video game explanation but I loved it. [laughs]

Jeff: Yes. My mind instantly went to Pac-Man-

Becky: Pac-Man.

Jeff: -eating M&Ms and it's just--

Becky: [laughs]

Michelle: She asked for a simple explanation. That's true. It's hard with genomes and things. It's really interesting to think about visually, and I think visual aids help a lot. We have some YouTube videos from our Pollinator Health Center website here at Montana State University that talk about how we detect viruses, how we quantify those viruses. If your listeners want to learn a little bit more and they have some visual aids rather than a Pac-Man eating an M&M, but that's a pretty good one, [laughter] then they can check those out.

Jeff: If you're looking for someone to come up with simple explanations for simple minds, that's me. If I can understand it, anybody can. We'll make sure we have those links in our show notes to the show. I think they'll be very useful. Where does this take place in the honey bee? You maybe contrast it to a human.

Michelle: Yes. A honey bee antiviral defense is probably centered in this organ called the fat body, which is the immune cell-generating organ of an insect. Since insects have an open circulatory system, and it's bathed in what we call hemolymph, which is essentially bee blood, those cells or hemocytes that make up the bee blood are going all over the bee and they're probably involved in antiviral defense.

We can compare and contrast that to the human immune system. A lot of the cells that are important for our immune system are produced in our bone marrow. They, of course, circulate through our lymph nodes all over our body, but they're also circulating in our blood and looking out for viral signatures. In the human immune system, typically, they're looking for viral proteins. We have antibodies that are ready to respond to viruses, particularly if somebody's been vaccinated against that virus or have had a preexisting infection with that virus then the human immune system is already primed up to defend us.

That's a protein-protein interaction, whereas the honey bee immune system that I described earlier was triggered by the nucleic acids inside the viral capsid. You and I also have that. If I was to inject double-stranded RNA into you right now, you would have what's called an interferon response or a massive antiviral response. We share that with honey bees actually. That double-stranded RNA, which is a replicative form of a viral genome, is just so potent it stimulates our immune systems as well as the honey bee immune systems.

Jeff: [laughs] Silence.

Michelle: Pretty crazy, huh?

Jeff: Yes. Silence.

Michelle: Earlier today, Jeff, you mentioned about I can't give a bee a vaccine. That's true because bees don't make antibodies or they don't make those proteins that would recognize a subsequent viral infection. We do in my lab give these little shots. We give them little shots with a glass. We hand-pull a little teeny needle from a microcapillary. We give them little shots right below their wing in their thorax. We do that so we can well control the amount of virus that we're giving a bee. When we need to study bee virus infections, part of our job is to infect those bees with a known amount of virus.

We do that, we call it the artificial Varroa destructor mite bite, where we take that little needle-- Varroa destructor, of course, transmits viruses naturally when it feeds on bees, and it can transmit them from bee to bee. We use little needles to give the infection in the laboratory setting. We can also give immune-stimulating molecules that way, double-stranded RNA. We can also feed them immune stimulatory molecules, but of course, I would never say we should give little bees their vaccine shots one by one with all the 30,000 bees in a colony, that's not practical, but for the laboratory setting, we can do hundreds of little bee vaccines in a day. It helps us get adequate results.

Becky: Michelle, how do you know their viral load pre-fake mite bite in order to compare it?

Michelle: This is a really good question. Really, if you're doing good science, you need to compare a virus-free group to the group that you gave a virus to the group that then you fed an antiviral to, for example, or something like that. In the case of honey bee research, this is really hard because we can't do blood draws on honey bees. We can't go and take a blood draw first, test it, and their viral status, just like kids at a daycare, could change any day. They could have an infection or not.

What we do-- Unfortunately, the students in my lab and other labs like mine across the world have to do extra experiments, basically. It's just by luck. In spring, our colonies have typically lower viral burdens, so we try to carry out a lot of our experiments, but when we analyze our data, we also look for 16 potentially preexisting or confounding infections retrospectively, then we just analyze the ones that have the least confounding infections first.

In some of the cases, if they all had, let's say, sacbrood virus, for example, I was studying deformed wing virus, but they all had sacbrood virus coming in, we'll quantify the levels of both deformed wing and sacbrood virus, and we can still examine our treatments compared to each other in a relative sense that way, but sometimes our experiments with honey bees are less ideal than they would be with cells grown in a dish or something like that because we do obtain our experimental subjects from the environments where they could have had preexisting infections. It's a very good question.

Jeff: Where is this going to take us down the road for the beekeeper, the work that you're doing, and the work that others are working on in the honey bee virology and the immune system? In 10 years, what will we be able to do for our bees that we can't do today?

Michelle: I think that's a great question and a really important question. Research in my lab at Montana State is really what I would call a basic science research lab. We're trying to understand the fundamentals of how the honey bee immune system works and then we hope down the road, or plan down the road, that in the long term, the better you understand a system, the better you can develop strategies to mitigate or lessen these honey bee virus infections.

One strategy I could think about right now for beekeepers, if I identify a gene such as bee antiviral protein-1, that's a gene and a protein we discovered in the lab, then eventually down the road, I could work with bee breeders such as Sue Cobey who is already rearing bees for honey production, gentleness, propolis production, name your list of traits, that often a lot of those traits are controlled by multiple genes.

I know that you guys recently had Brock Harpur on the podcast, a bee geneticist who's talking about traits that are controlled by multiple genes. Although we are not there yet, say, we identified a cluster of genes that we thought were really important for bees to mitigate or lessen viral infection, we could maybe clip the wing of that queen, and if the expression of that gene was higher, maybe you would select that queen to raise your next daughter queens from, things like that.

Bee breeding through selection would be one idea. We could also work on maybe some small molecule stimulants. Another area of research in my lab, which is funded by the USDA, is looking at the ability of phytochemicals such as thymol and thyme oil to stimulate the expression of these genes. Could we feed bees something that would boost their immune system temporarily and then give them the edge to combat their own viral infections naturally?

People have also looked at using RNA molecules, small inhibitory RNAs or double-stranded RNA. That's had mixed results in the field and not a super active area of research. Monsanto was looking into that for a while, but I think dropped that project for now. These are the long-term goals. Also in science, I think it's important for your listeners to understand that often, if you're looking for just the silver bullet to combat viral infections, probably that's not going to open your eyes to really understanding the system. This basic science is where a lot of times discovery happens and then serendipitously it'll result in what we wanted.

If you just look for a molecule that's going to combat deformed wing virus, you're going to miss a lot by not really thoroughly understanding the system.

Becky: One of the things, actually, I addressed it a little bit when we were talking to Sammy Ramsey about his work, figuring out what the mites were feeding on, the same idea is that right now you have a really good pulse on what we're seeing and the levels that we're seeing and you're getting to understand the trends. That wasn't going on in 1987 when Varroa first came.

Right now, I think because of the work you're doing, we're more prepared for that next virus that's emerging, and had people like you been around, really interested in bee viruses to a great extent, we maybe wouldn't have reached the level that we did with deformed wing, having it catch us by surprise. That was very long. You're shaking your head, so I hope [laughs] -

Michelle: Yes, it makes sense.

Becky: -you can comment.

Michelle: I guess, for your listeners, it's important to know that nearly every living organism has viruses that infect it. If they co-evolve together long enough, then just like the common cold virus, if we can deal with it, so can the bees because of their immune system. Unfortunately, before the mite was introduced to the US in the late '80s, we just weren't using those molecular tools for sequencing the viruses, characterizing the viruses in honey bee colonies like we do today, so it's hard to get this pre-mite, after-mite glimpse.

People have tried that, and often they do that at a snapshot in time, but when we team up with commercial beekeepers and have tracked viral loads at the colony level throughout time, the trends in any given colony of those virus abundance levels can shift on a weekly basis. Sometimes, good studies that just look at two snapshots in time, although you'll get data, is it the correct glimpse?

You also mentioned, Becky, there are lots of different strains, and deformed wing virus may or may not been such a problem before Varroa. I think that's a little bit yet to be determined honestly, but there are different strains of deformed winged virus. That means they have a different genetic sequence. Those may or may not have different virulence or affect the bees in different ways.

One thing that I think is really important because people can get really fixated on, is it deformed wing A or deformed wing B? Really, the actual picture out in the world is that there are several recombinant strains. That's when the viruses combine genomes. You have a mix of viruses out there that would be what we call in virology like a quasi-species cloud of viral sequences. That's pretty interesting.

They have a main sequence, what we call a consensus sequence. That's either A or B or some kind of intermediary recombinant virus. Really, it's difficult to tease out, especially when people have looked at the colony level in the past-- The majority of studies are done at the apiary level. You can just think of it now as Jeff mentioned, we're all a bit more virology experts since we've lived through the SARS coronavirus 2 pandemic. You can appreciate not everyone in your house got SARS coronavirus at the same time. Not everybody was affected to the extent that they were, and that's their immune systems kept checking in.

We have even less knowledge about that interaction between bees and their virus. We still have a lot to learn, which is great, but it might be undersatisfying for the beekeepers out there.

Jeff: The short of it is we're always going to be dealing with viruses.

Michelle: Yes.

Jeff: [laughs]

Michelle: It's just part of life. A cool thing about viruses that people don't know is I think everybody can picture those beautiful pictures of tulips that have a variegated leaf that's white in some areas and red in others, a beautiful tulip. French painters painted them. That modeling we call that is due to a virus, tulip breaking virus. Viruses get a really bad rep, but maybe some of them they make us stronger. We have a better immune system. Some of them just go away and we never know we had them.

We only study the viruses that are really bad or that cause infections that make us sick, but there are a lot of virus infections that infect every organism that is maybe not less detrimental. Some even enhance drought tolerance. Again, another plant example. Yes, they're really interesting.

Jeff: Somewhere during the COVID years I heard someone say that the viruses are the cause of evolution. Without viruses, there would've been no evolution. That's a neat way of thinking of it.

Michelle: Yes. There's actually a hypothesis called the Red Queen hypothesis in virology and just immunology in general, where it takes all the running that you can to stay in the same place. That's trying to describe that interaction of between the virus evolves, the host evolves, the virus evolves, the host evolves, and that's a continuous cycle. You're running in the same place, basically.

Jeff: That's really fascinating.

Becky: I would love to hear a snapshot of what work you're doing with the Pollinator Health Center.

Michelle: We have a pollinator health center here at Montana State University. We have several researchers investigating pollinator health, including myself who specializes in honey bees, of course. Dr. Laura Burkle is here. She's a bumblebee specialist, wild and native bee specialist here in Montana. Dr. Mike Ivie and Dr. Casey Delphia are studying the wild bees of Montana, figuring out what hundreds of different native and wild bee species live here in Montana. That's great. They're describing new ranges for bees that they just didn't know were here, as well as discovering new bees here in Montana. That's pretty exciting.

We also have people that study alfalfa leafcutter bees, Kevin O'Neill. We have a group of us here that are interested in pollinator health.

Becky: Are you the only one looking at viruses and are you being asked to look at viruses in native bees?

Michelle: Yes. I'm the only one who's here at Montana State that's looking at viruses. Then the question is an important one. One of the coolest and probably most interesting area of research is that in honey bee virology, and this is where we should back up and think of these as just bee viruses, is the ecology of bee viruses. Unlike human viruses, the viruses that infect honey bees can infect a broader range of insects, that includes bumblebees, ants, wasps, so we really do need to think about the ecology of these virus infections, not only winter and how are they transmitted.

There's evidence to indicate that they're transmitted on floral resources. Most of my work looking at viruses and other insects, particularly bees, Andrena, has been done in Israel in collaboration with a team there. We look at viruses that are both in wild and native bees in a certain area as well as with cohort foraging honey bees. In some cases, those viruses are going to be greater in the honey bees at that particular point in time or lower in the Andrena. Then there's going to be vice versa.

Understanding those transmission dynamics. One of the things that came from that study in Israel as well as others here led by Diana Cox-Foster and many others looking at this here in the US is transmission events maybe can be lessened the more diverse floral resources you have, because honey bees are of course generalist pollinators, they're going to be visiting everything, where Andrena, they love yellow mustards, so they're going to just be going there. If we can dilute those transmission events, maybe that's something we can do at the landscape level to mitigate those virus transmissions.

One of the things I really hope that scientists and beekeepers avoid is this blaming or this directionality thing.

[laughter]

That's really hard to tell. The use of the word spillover, in my opinion, just isn't even accurate for this, I would say intergenus or intergenre transmission and this bee virus ecology. We mentioned already that we have a lot to learn about the interaction just between these viruses and the honey bees, now think about it at the community ecology level, we have even a lot more to learn there, but I think that's a very exciting and important area of research.

Jeff: The spillover effect that concern causes a lot of debates where it really shouldn't happen at this point.

Michelle: I think at this point in time we can err in the side of caution. If it's the last few holdouts of where the rusty patched bumble bee is, okay, let's give them their space. Let's not bring in a lot of newcomers to their areas. I think in general, we really have a lot to understand yet about the virus transmission out in the environment.

Jeff: Let me ask you, as we're coming up towards the end of our time here, as a honey bee virologist, what keeps you up at night?

Michelle: Honestly, and probably this is the truth for beekeepers too, the pace of research is pretty slow. As Becky and I were discussing, we have a lot of experiments that have confounding infections and so getting those clear-cut answers is harder on honey bee system. It takes a lot of time and resources. I like to always mention when I give public talks that this is your taxpayer dollars at work.

My research is funded by the National Science Foundation and the United States Department of Agriculture. Without those taxpayer-funded research support dollars, there'd be nobody investigating these viruses and their impact on bees. Thank you all out there for supporting research, it's really important. The pace goes a bit slow, and you're right, after nearly 10 years of research on honey bees and the viruses that infect them, I don't have an antiviral for you.

I can tell you to keep your bees in areas that have diverse floral resource, keep your mite infestation levels low because we know mites vector viruses, but importantly, mites don't drive the pattern of all the viruses that infect bees and so even if you have low mites-- I hear this from beekeepers a lot, "I kept my mites down and I got my virus report back and I still have viruses," then they feel bad about that. You shouldn't feel bad about that. Not all those dynamics are governed by the mites. Viruses are out there and in the environment and they're really common and a naturally occurring interaction with bees

Jeff: Throw on top of that exposure to hard pesticides and the long-term effects of low-dose pesticides. You really have a big evolving moving Pac-Man game going.

Michelle: Yes. We did a little research on that too with Montana Department of Ag Specialty Crop Block funding, that's a very important funding source as well for us, looking at sub-lethal doses of agrochemicals. What we found is that some of those reduce the expression of those immune genes that are so important for honey bee antiviral defense, and then their virus abundance was then slightly higher, and so we think that that interaction with chemicals in the environment could negatively impact the bees immune response, thus the viruses may be a bigger problem then.

Jeff: That was adult bees or was that with the larvae too?

Michelle: We've really just focused on adult bees in my lab, but I know others have looked at larvae, particularly Dr. Francesco Nazzi in Italy, looking at some of those chemical exposures and larvae and mites and viruses and things like that, so people are looking at that as well.

Jeff: Is there anything we haven't asked you that you are prepared to talk about and just we didn't ask the right question?

Michelle: Oh, yes. You asked a lot of really great questions.

[laughter]

You got to be great students in my virology or geneticist class. Love to have you anytime.

[laughter]

One of the things we didn't get a chance yet to talk about is Project Apis m. Of course, a nonprofit organization that supports bee research, gives best practices, management guides, does a lot for bee science in general. I'm a scientific advisory board member for Project Apis m. and students in my lab have benefited by getting a scholarship, which is primarily funded by Costco, interestingly enough. I just think Project Apis m. is a really great organization that supports bee research. Probably your listeners would benefit by checking out their website and the materials online. That's the last thing I wanted to mention.

Jeff: Project Apis m. is a wonderful organization. We've had them on the podcast. We should get them back. It's been a couple of years since we've had them on, but yes, thank you for mentioning them. We'll definitely have a link to their website in the show notes.

Becky: Michelle, can I ask you one last question?

Michelle: Oh, for sure.

Becky: How do you clean your hive tools?

Michelle: Oh, yes. That is an important practical thing. Going from colony to colony, we definitely put them in the smoker first so that we're not transmitting any viruses or other microbes between those colonies. Then occasionally, I guess we scrub them off, but that's really occasionally, so really it's just putting them in the smoker for the most part is all we do. We have only one yard too, so I think the importance of cleaning your tools between different yards is even more important.

We only have about 10 colonies. We use those for experiments in the lab. Whenever we want to ask a bigger question, we always team up with beekeepers that have hundreds and thousands of colonies because they're the real experts at keeping those bees. When we're doing epidemiologic studies, we always team up with those. We don't study my MSU bees. [laughter]

Becky: Excellent. Thank you.

Jeff: I'll say that for anybody who's putting their hive tool in the smoker, make sure you pull it out with a gloved hand or ask your bee buddy to pull it out because you'll do that once and realize it's not a good thing.

Michelle: Good point.

Becky: Jug of cold water that works too, or snow, if you have snow around you. [laughs]

Jeff: Michelle, thank you so much for joining us this afternoon. I'm sure our listeners learned a lot. I look forward to having you back. We could actually start a podcast about honey bee virology, I think, and just have episode after episode because this is such a fascinating topic.

[music]

Michelle: Thank you very much for having me. It's been fun. I would love to come back anytime. Thank you, guys.

Becky: Thanks so much, Michelle.

[music]

Jeff: Michelle made virology fun. I found that conversation entirely fascinating.

Becky: Absolutely. I'll admit I'm glad there's not going to be a test after the podcast because she is so smart, and although she very clearly explained the information, I'm just looking at the notes that I took and that was a lot of great, great important information broken down very nicely, but I still don't want to be tested on it.

Jeff: [laughs] No. Unless it had to do with sorting the red M&M's from the blue M&M's and the green M&M's, I wouldn't understand it, but it's so important, as we've all learned through the COVID years, even today, how important viruses are, not only when we get sick and we get a runny nose, but just how life functions here on earth.

Becky: I just loved the information about Project Apis m. and Christi Heintz being key to recruiting her over to the side of honey bee health and viruses. That made such a difference. It's so very important because, with the work that she's doing, she's collecting data and doing research, but she's training students to do the same, and some of those students will go out there and continue their research careers and support honey bees. It's so important that there was a need for more virus information and more research. It's not just being done, but it's being amplified through the work she's doing at her university.

Jeff: If you're like me and didn't get enough of this information about virology and viruses and honey bees, Michelle did tell us after we stopped recording that she was recently on another podcast talking about viruses and honey bee viruses. The podcast name is  This Week in Virology. We will have links for that in the show notes. I think it'll be a really good show.

[music]

Becky: Absolutely. Looking forward to listening to that one too. I feel like I'm ready for it now.

Jeff: [chuckles] I might understand it. That about wraps it up for this episode. Before we go, I want to encourage our listeners to follow us and rate us five stars on Apple Podcasts wherever you download and stream the show. Even better, write a review and let other beekeepers looking for a new podcast know what you like. You can get there directly from our website by clicking on the reviews along the top of any webpage. We want to thank our regular episode sponsors, Betterbee, Global Patties, Strong Microbials, and Northern Bee Books for their generous support.

Finally, and most importantly, we want to thank you the  Beekeeping Today Podcast listener for joining us on this show. Feel free to leave us questions and comments at the "Leave a Comment" section under each episode on the website. We'd love to hear from you. Thanks a lot, everybody.

[music]

[00:49:44] [END OF AUDIO]