Viewscapes

Bats and viruses

January 27, 2021 Washington State Magazine Season 1 Episode 6
Viewscapes
Bats and viruses
Show Notes Transcript

Bats could be a key to help prevent a future pandemic.

Washington State University researchers Stephanie Seifert and Michael Letko explain why the flying mammals are important for improving our understanding of viruses and diseases that spill over from animals to humans, such as Ebola, Middle East Respiratory Syndrome (MERS), and SARS-CoV-2 novel coronavirus that causes COVID-19. Seifert and Letko also take on misconceptions about the pandemic and talk about the challenges of studying bats.

Both scientists work in the Paul G. Allen School for Global Animal Health, where Seifert is a research assistant professor studying molecular ecology.  Letko is an assistant professor and molecular virologist focused on cross-species transmission and viral-host interactions. 

The Allen School leads global research of zoonotic disease transmission between animals and humans. The school is also part of the One Health effort to further the understanding that human health is directly related to the health of animals and the surrounding environment.

WSU News science writer Sara Zaske is the guest host.

Read more about Letko’s coronavirus research in “Viral haystack,” Washington State Magazine, Fall 2020.

[Thank you to Felix Blume for the recording of bats in Southern France.]

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Stephanie Seifert:

There's been a lot of focus on whether or not bats are unique in that they have a lot of zoonotic pathogens. Not so much that each individual bat species carries a lot of pathogens or more pathogens relative to other groups of animals, instead it's more that there are a lot of different bat species.

Larry Clark:

That's Stephanie Seifert, a researcher at Washington State University examining viruses that can spill over to humans from bats and other animals, like the novel coronavirus that causes COVID-19. You're listening to Viewscapes, stories from Washington State Magazine, connecting you to Washington State University, the state and the world. I'm magazine editor, Larry Clark.

                Seifert and her colleague Michael Letko from the Paul G. Allen School for Global Animal Health spoke with our guest host, WSU science writer Sarah Zaske, about bats, viruses, and pandemics.

Stephanie Seifert:

Sure. I'm Dr. Stephanie Seifert. I am a new faculty member, a research assistant professor in the Paul G. Allen School here at WSU. For the last few years, I have been working largely with bats in Republic of Congo, looking for different zoonotic pathogens that bats carry.

Michael Letko:

My name is Dr. Michael Letko. I'm a new assistant professor at the Paul Allen School as well. My work is mostly focused on looking at the smaller details of how viruses transmit between species, and so far this is focused largely on bats and more specifically on the coronaviruses that bats carry.

Sarah Zaske:

My name is Sarah Zaske, I'm the science writer for WSU News. Broadly, why should we study viruses in bats? Why is it important to look at them?

Stephanie Seifert:

I think bats and rodents are the two groups that I'm most interested in looking at in terms of being reservoirs for different types of pathogens, zoonotic pathogens that might spill over into humans or pathogens that might spill over into wildlife or livestock or domestic animals. I think that there's been a lot of focus on bats recently. There are some pretty big pathogens that we're all interested in. Of course, SARS-CoV-2, which is the agent of COVID 19, is a big one right now that everyone has on their minds, but there are several other coronaviruses that have spilled over from bats. For instance, Middle East Respiratory Syndrome-related coronavirus in the Middle East is a big, longstanding issue since about 2012. There are also researchers here in the Paul G. Allen School who are also looking for MERS coronaviruses in camels in Kenya.

                There's been a lot of focus on whether or not bats are unique in that they have a lot of zoonotic pathogens. I think that the issue is a little bit different from that. It's not so much that each individual bat species carries a lot of pathogens or more pathogens relative to other groups of animals. I think instead it's more that there are a lot of different bat species, and they interact often either directly with us or indirectly with us. And so for me it's more about identifying those interfaces that allow for a zoonotic potential, where you have pathogens in a species, and then there's a potential for exposure to humans or to wildlife or livestock. For instance, MERS coronavirus spills over into camels, and then that's been kind of the interface now with humans.

                Rabies virus is another one, where rabies virus... We think about it as being a bat pathogen, but really most of the human cases are from domestic animals like dogs or cats or sometimes cows. And so I think that it's just identifying where we have that opportunity for spillover is really important.

Sarah Zaske:

Michael, do you want to tell us a little bit about how you began studying coronaviruses? Both of you worked at the Rocky Mountain Lab in Montana, is that right? And what did you guys do there?

Michael Letko:

Yeah, so my work at Rocky Mountain was applying the concepts and stuff that I had been working on in grad school. In my thesis work it was a lot of how viral proteins interact with host proteins. In order for these viruses to replicate, they need to be able to interact with all kinds of host cell machinery. When it came to RML, there's opportunity there to work on viruses that you maybe can't work on in other places, so that was my foot in the door with the coronaviruses and working with those in the BSL-3. The coronaviruses were really... They got a lot of my attention initially because each one of them seems to have its own unique story of how it was transmitting between species. There's a lot of opportunity when we're thinking about these viruses having to interact with numerous different hosts. There's just so much to study that was really the open-endedness that the coronavirus has presented. There's so many of them, they're in so many different animals, and they move between them. So for somebody like me wanting to study how these proteins are interacting, that's just a ripe source for it.

Stephanie Seifert:

I think where Michael has been working on that very fine scale interaction at the molecular level, my focus had been on more populations and ecology. For the last few years in the virus ecology section at NIH, I was leading the field effort to sample bats and other wildlife for Ebola viruses in Republic of Congo. Ebola virus is one of those other things people consider a bat virus, but we don't actually know what the reservoir species is. After something like 40 years since its discovery, we still don't actually know which species of bat, or if it is indeed a bat, that is that contact point between humans and wildlife that leads to infection. Even after all these years, we still don't know where Ebola virus comes from. I can identify lots of different viral species and then Michael can take that data and start figuring out which ones actually have the potential to enter human cells.

Sarah Zaske:

The question we all want to know is how do we prevent this from happening again? What do we need to do as a research community?

Michael Letko:

I guess there's probably a number of ways we can start to address this issue. I think these are long standing questions that scientists have been working on since we found viruses lingering in wildlife, really. How do you prevent that? There's the classic... There's the kind of approaches that we're more familiar with, such as vaccines and trying to vaccinate wildlife and trying to vaccinate ourselves against various pathogens and viruses circulating in nature.

                But then there's stuff that we can learn more from the type of work that Steph does, where we're learning about the host biology itself that allows us to take intervention. If we can identify the reservoir hosts for these viruses, for example, then we can start to put in measures to maybe keep distance between ourselves and our domestic animal populations from some of these reservoir species, for example. And I think Steph probably has some more examples of that. But yeah, there are lots of avenues, many of them are being explored, but most of them are still in their nascent phase I think at this point.

Stephanie Seifert:

I think that we can potentially start to identify where we think these spillovers might happen. I think there are groups who were predicting another SARS-like coronavirus spilling over into the human population for a long time, but still there's a lack of information on how that spillover exactly takes place. So for SARS-CoV-1 back in 2003 and 2004, there's strong evidence that that spillover occurred basically from bats into civic cats, and then civet cats into humans at restaurants. A very tangible interface. But for SARS-CoV-2, we still don't know. We might not identify their reservoir species for that virus still.

                I think that first is identifying what we think of as risky interactions or risky pathogens that we want to keep an eye on, but actually preventing any spillover, I think is not going to be the goal. The goal should be to prevent spread through early detection and then control. An example I always like to put out is there is a Sudan virus, which is a type of filovirus closely related to Ebola virus, causes hemorrhagic fever. There was a spillover event in a very rural community, and the nurse who first saw the patient, identified it as a viral hemorrhagic pathogen and then treated the patient as such, so we're... PPE and then immediately [inaudible 00:09:15] the body. They treated it as being a viral hemorrhagic disease before they actually had confirmation of what it was, and that was an outbreak of one. So I think if we can try to mitigate the spread the human-to-human transmission, then that's a big thing.

                If we know that there's a pathogen that's a risk... So in Australia, for instance, Hendra virus is a Henipavirus that causes, again, very severe pathology, very high mortality rate. That virus spills over from fruit bats into horses. Horses get respiratory disease, and then that can essentially transmit to humans, and then that's when you have human cases. So now there is a vaccine for horses in Australia against Hendra virus, and we also have started to identify points of contact between the horses and the bats. The bats will roost in a fruit tree that's in a pasture with horses, the horses are eating the fallen fruit underneath of the bats, the bats shed the virus in the urine. Now we know this whole transmission cycle and we can start to mitigate, either by fencing off those trees so that the bats and the horses no longer interact. We do have a vaccine for horses now, but the compliance is surprisingly low for people actually vaccinating their horses against Hendra virus.

                I think that there's a lot of strategies that we can take that are maybe a little bit lower costs than trying to retroactively, after we have something like COVID, where it's on the global scale... We can't easily do contact tracing anymore and just isolate a few individuals to prevent further spread. I think it's more about mitigating those earliest stages of a pandemic and preventing it from actually going beyond the point of that first initial spillover, or if we can prevent this spillover, but with 10,000-something viruses, we don't know how many are going to have a zoonotic risk. So I think we always need to be prepared for the idea that something can spillover that's new. We just have to be better about detecting it and then trying to control it early.

                We still can't answer even basic questions like... We have bats that we know don't have severe pathology after exposure to, say, Nipah virus, which causes severe pathology in humans and in lots of other species, or Hendra virus, it's the same thing. We just don't see a strong pathology in the bats that are the reservoir.

                There's some question about how the bats are not having that very strong inflammatory response... Whether or not they actually clear these viruses, if they're just not very good at viral clearance, because we often see that bats will shed virus for a period, and then if we hold them for a long time in the laboratory, that sometimes they'll end up shedding that virus again seven months later, which is something they observed with Marburg virus at the CDC when they held bats for, I think, 17 months. So it seemed to persist in that population, suggesting some kind of incomplete clearance in those bats.

                All of these things, we still don't actually understand those mechanisms. I think that that's a really active area of research that... It would be really helpful for us to better understand those factors, so that we can also then maybe identify why some of these viruses are so pathogenic in humans, if that's something that's driven by the immune response and bats or not. But also to better understand some of the field data that we acquire and see if that actually helps us to narrow down species that might be the reservoir for some of these viruses that we haven't identified the reservoir for, like Ebola virus or like SARS-CoV-2.

Sarah Zaske:

It sounds like there's not a tremendous amount known about bats, so what are some of the challenges to studying them?

Michael Letko:

In the laboratory... I think Steph actually has maybe the best experience with working with bats in the laboratory, but just the fact that we don't know many of the reservoir species themselves is a huge challenge, because then which bat do you pick to try to study if you want to take these kinds of experiments into a laboratory setting? So just from what we can control and from controlled experiments, it's challenging without knowing the species that are truly involved, because bats are so diverse. Then I got a... Steph can probably say more even about the challenges working with them in the field as well.

Stephanie Seifert:

The big problem that we have is tools. The molecular tools needed to study the immunology of bat just... They don't exist yet. So a lot of the tools that we have for studying immunology are developed for model organisms like rodents or non-human primates. So mice, there are a lot of different tools where we have assays that can target very specific types of immune cells, and we don't have those tools for bats yet. That's something that is, I think, really challenging to develop, and it's definitely something that I've been talking with a few different folks about... How do we start to address those questions? Because my training is more in molecular ecology and less on immunology. It's more of like... I see that this is an important question, so collaboration with experts in very different fields is definitely going to be necessary for us to start to approach some of those bigger questions.

Michael Letko:

I think, to elaborate on that and come back to the species issue, what we kind of... Maybe an underlying assumption here is that the bats themselves are incredibly diverse. So when we are talking about one species or another, it's not like... If we develop the tools and reagents needed to study one species, it may not be applicable to any of the other species. So from even a practical standpoint, when Steph is saying we don't have the immunology reagents, even if we wanted to start just making them, you pick what, one of a thousand different species, and you hope that that's the most relevant one when we know that that's not the case. The diversity of bats also works against us when we're trying to standardize and come up with these types of things.

Sarah Zaske:

It sounds like a huge task. One question that always comes up in the media is they trace the SARS-CoV-2 epidemic back to China. Could this happen elsewhere? Is it limited to certain geographic regions?

Michael Letko:

There's no reason to think it wouldn't happen elsewhere. Coronaviruses for example, are widely distributed in a lot of... It's not just China. And that's coronaviruses, right? You look at filoviruses, which include Ebola, and you find them more wide-spersed beyond central Africa. So the viruses themselves are not necessarily always geographically restricted. Maybe that specific virus is, but it's one in a sea of very similar relatives.

Stephanie Seifert:

"Zoonotic transmission can happen anywhere" is one of my most common phrases, like if a strange dog comes up at the dog park and licks my face, I'll turn and say, "Zoonotic transmission can happen anywhere." But even in 2009 we had the swine flu, which was a new re-assortment of Influenza virus that spread really rapidly throughout the world.

                The Paul Allen School for Global Animal Health, just that we're global. Stuff is moving all over the world all the time through the animal trade. We ourselves are moving all over the place all the time. So I think even when you have an origin point, that pathogens can move so quickly now all over the world. It can take maybe 12 or 15 hours to hop to the other side of the planet. Yes, this specific type of SARS-like coronaviruses, we know that there are a lot of them in China, but there's also SARS-like coronaviruses or sarbecoviruses in Africa, and I believe now in Europe as well. We just haven't really looked for them very much in the U.S. for that kind of lineage, but we know that beta coronaviruses are, again, all over the world. Even MERS coronavirus has caused outbreaks in South Korea, not just the Middle East. So I think that with our global world now, that these viruses can emerge anywhere and they can get anywhere.

Michael Letko:

And viruses do transmit and cross species in, let's say, the United States as well, right? We have those hantaviruses that hikers are coming into contact with. It happens. It happens in a lot of places. There's nothing saying-

Stephanie Seifert:

Yeah. It's possible that we'll have a hantavirus that has a higher rate of human-to-human transmission, in which case, that could come from the Pacific Northwest. We have several cases of hantavirus in Washington state every year, which is a zoonotic pathogen transmitted through the urine of rodents. Certainly this specific pathogen started in China, but there are zoonotic pathogens all over the world, and they're always spilling over into humans.

Sarah Zaske:

With so many viruses out there and different animals out there, is another pandemic inevitable?

Michael Letko:

Basically, yes. Basically, yes. We don't know all of the viruses that are out there. We don't know even if the next pandemic, if it's going to be a virus or if it's going to be a bacteria or something else. But I don't know. I think if anything, SARS-2 shows us that this stuff continuously happens. Our modern society is susceptible to the same things we were susceptible to in the dark ages. It's a continuous thing. It's a repeated aspect of life.

Sarah Zaske:

To put a more positive spin on it, Stephanie was talking about this earlier. What kind of steps can we take? If we can't prevent it, what can we do to minimize it?

Stephanie Seifert:

We can't prevent outbreaks, which is at initial spillover and then some spread. But I think if we can detect things early, which means sometimes just having the capacity and the institutional knowledge throughout the world to be able to test for a wide variety of pathogens, and that kind of long-term investment for surveillance I think is really important. But also targeted surveillance where we understand the most risky types of interactions. We know, for instance... We do a lot of surveillance for avian flu at poultry farms. So avian influenza, we know that that's a risky interface, and we're really good at detecting it early now and then controlling so that we don't have a pandemic but we just have a small limited outbreak. I think a great example is even here at the Paul G. Allen School where we have the rabies virus efforts to eradicate rabies. A lot of that is through vaccination of domestic animals, like dogs and cats, where we know that that's a risky interface for humans. Most humans contract rabies virus from dogs and cats and not from bats.

Sarah Zaske:

Is there anything else that you could tell us about what kind of projects you have underway, maybe ones you haven't talked about yet?

Stephanie Seifert:

I think Michael was giving me a little plug, so I do plan on take some hantavirus work in the Western United States. I think that that's really important to be able to do that kind of community and local engagement, and also start addressing a potential issue that we have here in Washington State, for example, where we know that there are several deaths each year attributable to hantavirus, and just better understanding how to mitigate that kind of spillover here in the U.S. But also just better understanding the diversity of hantaviruses and rodents here and how, for instance, land use change can influence pathogen maintenance in these rodent populations. What about you, Michael?

Michael Letko:

Up to this point, I've been looking a lot at the variation in the viruses and how that affects those virus's ability to get into the host. But by the same question, one thing that we're learning now, especially with the work that's coming out around SARS-2, is that the host themselves. Some of these bats are actually variable within the species, so that not all of the bats within a species are susceptible or capable of transmitting these viruses.

Sarah Zaske:

There's been so much news around the coronavirus and COVID-19. What is one of the biggest misconceptions that you see played out over and over that you would like to correct? Or what do you find yourself correcting your friends and saying, "No, that's not quite right?"

Michael Letko:

Getting at that bigger question of where these viruses come from. It's really frustrating when people are saying that it's an engineered virus and a manmade virus, when literally there are whole careers and this is a field of study. It's very clear that these are natural viruses. Humans are terrible and mean in our own way, but I don't think this is the case where we have that for now.

Stephanie Seifert:

I think one thing is there's also a little bit of the origin. Because we don't necessarily know which species or how exactly it spilled over, or even potentially the exact location where that spillover occurred. That kind of jumped to that, "Oh, well, it's something really devious, and it was an engineered thing." It's a tragedy, and it's hard to wrap our heads around because it's affecting so many lives, but that doesn't mean that it was some kind of intentional evil thing. I think that these pathogens are a risk, and having long-term collaborations with groups like EcoHealth Alliance and NIH and the Wuhan Institute for Virology... That's why we so much about these pathogens. I think we had a head start in developing monoclonals or testing different types of therapeutic agents early on specifically because we had so much information and long-term collaboration after the SARS coronavirus outbreak.

                There's also been, I think, a lot of effort in developing vaccines against the MERS coronavirus, which is a related coronavirus. So I think all of these big global collaborative efforts to study these viruses before we had the pandemic have really helped us in developing therapeutics after we have the pandemic. There's still a lot left out there that we need to be aware of and researching and preparing for in case we ever do have a spillover event, so then of course, that early detection is really important.

Larry Clark:

Thanks for listening to Viewscapes. You can learn more about the Allen School's global health research at globalhealth.wsu.edu. Our theme music was written by Greg Yasinitsky. The sounds at the beginning were hundreds of bats in the south of France, screaming at twilight, recorded by Felix Bloom. For more stories from Washington State University, visit magazine.wsu.edu.