S6 E4: Little Bunny Foo Foo: The Story of Rabbit Hemorrhagic Disease Virus

0:00 During March of twenty twenty, I did what so many of us did during that time. I took up a new hobby. I decided that I was going to propagate plants. I bought all kinds of seeds. I had the idea that I could grow any kind of herb that I wanted, and I would be able to use these herbs to do everything from infusing oils to throwing them on some amazingly tasty meals. Well, I failed miserably. I had no idea what I was doing, and most of my plants died. I didn't know how to start them correctly, I didn't know how to cut them correctly. So there I was with a bunch of empty pots, starting over and over again, and failing every time. Then I found true Leaf Market.

0:50 True Leaf offers seed packets, grow kits, and even planters for roughly the same price that I was paying at the local stores. Seed packets started about two forty nine and organic seeds start at two ninety nine. For the last fifty years, true Leaf Market has offered a huge selection of non GMO seeds, including vegetables, grains, flowers, cover crops, specialty seeds, sprouting and microgreen seeds, and of course my favorite herbs. They offer heirlooms, organics, and hybrids of all kinds too. With super fast shipping and free shipping on orders over seventy five dollars, you can't go wrong. No matter whether you're an in home gardener with grow lights and raised garden beds in the living room or a bulk wholesaler, True Leaf Market is the place to look for all your seed needs. Remember all those past failures that I had, well, True Leaf Market has my back with growing supplies and starter kits.

1:53 Plus they have a ton of how two PDFs that I can download to my computer with all the info I need to be successful with my herb garden. I'm already more successful than I have ever been. I want you to succeed in your gardening ventures too, so I'm teaming up with true Leaf through June thirtieth to offer you ten dollars off any order of fifty dollars or more when you use promo code cod ten. Go to www dot true leafmarket dot com and use the promo code cod ten for ten dollars off any order of fifty dollars or more, and don't forget You'll also get free shipping on orders of over seventy five dollars. This offer is only available through June thirtieth, so get your seeds today and have a great gardening season. My name is Keely and I host a true grimin paranormal podcast called Missy Mysteries. Missy Mysteries takes a special focus on unsolved cases. I'm missing Person's Case. All of my truecrime episodes are made and hopes to raise awareness and bring justice to those who need it most. Most of these episodes are made in partnership or made with the families of the victims and missing people. But the podcast isn't always true crime. Sometimes I bring spooky content like countings, aliens, and cryptics such as the original story of the Conjuring House, The Life of Edin lur

3:23 and Warren and Mothman. Truecrime and paranormal even cross at times to make two part episodes like The Bobby Mackey Music World, The Lizzie Bordenhouse, and The Veliska Acts Murder House. Missy Mysteries is ready to be binge listened to with over fifty episodes anywhere you get your podcasts. I cannot wait to keep you company whenever and wherever you like to listen to your podcast. Hi, this is Kelly and this is Jenna. We're the hosts of ODFN. That's why from Murder. Each week we discuss a true crime murder case and intertwine our unique sense of dark humor. Each episode relates to a word starting with the letter D. The stories we tell are serious and true. Our opinions are not. But be warned we don't hold back on the details of the case or our inappropriate comments and colorful language. Join us every Monday on your favorite podcast provider for a new episode of ODFM. You're on a full ride scholarship to Hell Dark Cast Network. Come on over to the dark Side. We're really nice people once you get past the true crime and scary science. Hello, and welcome to Cause of Death. One hundred seconds to midnight. I'm your host, Jackie Moranti. I want to begin this episode by thanking all

4:56 of my long time and new listeners for stick with this podcast. You are the reason that I pour over pages and pages of white papers and government documents so that every two weeks I can tell you about another disease or another disaster that plagues the earth. It's because of you that I made it to number fifty five on the Apple Podcast charts for Life Sciences in the US. I've also stayed at number one on the Good Pods Life Sciences and Indie Life Sciences charts for several weeks now. And if that wasn't enough, I've hit the top five percent in the Listen Notes charts. All these things mean that the podcast will be easier to find for other listeners. Every chart I make, every subscription, every review, they all count toward making this podcast the first thing that comes up when people look up cause of death in their podcast player.

6:00 It's a big deal, and if it weren't for all of you, I'd just be talking to myself. So thank you so much for supporting this project. If you're new to the pod, I'm going to ask that you don't give up on it. It's a little technical in the beginning, but I promise by the time we get to the history part of the episode, everything will seem a lot clearer. I also want to say that this is not as depressing as it seems. I won't give your rose colored glasses, but I will try to give you a greater understanding of the things that can be done to bring us back from the brink. I had a couple of listener emails after the last show. My friend and mentor Eric had some very kind words for me. I even got a little misty over this. I love that I can have you research all the stuff that I have questions about.

6:55 I might have to wait a few months, but you get there, and I'm grateful. I'm also pissed off about the deregulation of trains. Thanks so much, Eric, I appreciate those words, especially coming from you. Eric has one of the best true crime podcasts around. It's called True Consequences. I do quite a bit of research and writing for that show. So if you love this one and you love true crime, go listen to Eric and you'll hear more of my research. In writing in those episodes, Jessica wrote, are you sure that the railroads are totally under their own control? No one oversees them. There is no federal agency telling them what they can and can't do. Okay, Jessica. Nothing pisses me off more than finding out that any entity governs themselves. That's a golden invitation for corruption. But the railroad has been self governed since the first tracks were laid. That information is out there for anyone who looks for it, and also it's in the show notes of the last episode. Dominic asked, why is it taking so long to figure out how these disasters are affecting ecosystems? Does it really take forty years to find out what happened at Chernobyl? How can they not know what happened to the larger wildlife in Ohio, Okay? So Chernobyl is a

8:26 strange beast. Remember, Russia didn't immediately tell the rest of the world that there was a problem. They tried to hide the whole incident and clean it up on their own. Then the area around that plant for miles was contaminated, and no one knew whether it was safe to go into that area or not. People still don't live in the sea easy. The immediate effects weren't studied until years after the accident, and that was partly because the Russian government wouldn't let anyone in. Even after the xon Valdis, the effects of that spill on wildlife weren't totally appreciated for years after the spill. It takes several generations to see what lasting damage has been done. The Xon Valdis didn't take quite as long as Chernobyl, but it still took several years to determine which species would bounce back and how long it would take. They also had to figure out what long term damage was done to the food chain. We'll have to see what Ohio breaks. That will depend on how the railroad handles it.

9:37 So far, they've been rather combative when people come in to do any research on the environment. They don't want the world to know how badly they screwed up. My last thanks go out to those who just rode in to say how much they're enjoying the Who's Who outside of the Zoo season. Some of you asked if this would be the only season an addressing wildlife, and the answer to that is no. At some point I'll do a who's Who outside of the zoo too. There's a lot to talk about when we delve into wildlife conservation and the environment. With that, let's get into rabbit hammorrhagic disease. Will begin as usual with ideology and pathology. Rabbits, hairs, and pikas belong to an order of animals called lagomorphs or order Lagomorpha. Rabbits and hairs belong to the family Leporidae, and pikas belong to the family Ochotanidae.

10:41 While rabbits and hairs have long ears, a short tail, and very strong hind limbs that give them that characteristic bounding motion, pikas are smaller. They have shorter, rounded ears and no external tail to speak of, and they also have smaller hind limbs that give them more of a scam bring motion. Lagomorphs are small to medium sized herbivores that tend to live underground. At one time, they were included in the order Rhodentia, since both orders possess a set of incisors that grow throughout their lives. However, lagomorphs also have a second pair of incisors that are set directly behind the growing pair in the upper jaw. This trait is specific to lagomorphs. Now, thanks to species gene coating, we know that these two orders have very distinct and separate evolutionary histories. A right, so we're back to talking about poop for a minute.

11:41 I know, I promised that I wasn't going to mention poop for a while after the restaurant rogue season, but lagomorphs have a definite poop trait that defines them. They produce two kinds of feces, the solid round droppings that we all know is rabbit poob and softer, grease like pellets. This is important to the survival of the order because the softer feces hold up to five times the vitamin content of the hard feces. These feces are produced in the secum and are re ingested so that the animal can get all the nutrients out of the food they eat. The double digestion process allows the feces to be passed through the system twice so that they can get every bit of the vitamins and minerals out of their food. Of course, rabbits reproduce like well rabbits.

12:41 Many species have several large litters per year, but there are some species that only reproduce once a year and have very small litters. Rabbits are not great moms. They leave their young for most of the day, only coming back to nurse once or twice for a really short time, but their milk is among the richest of any mammal, and their young grow quickly. They generally wean in about a month Rabbits play an important role in the food chain their food. The average life expectancy of a wild rabbit is about nine months.

13:22 There are about twenty nine species of piica. These animals are found in the mountains of western North America and Asia. The two species of North American pikas and several of the Asian species live in rocky habitat so they don't burrow. Like rabbits and hairs, there are around thirty species of hair and twenty eight species of rabbit, and they exist worldwide. Now that we know what we're dealing with, let's talk about the disease that's specific to lagomorphs. Rabbit hemorrhagic disease virus. Rabbit hemorrhagic disease virus is a highly infectious and fatal disease of the European rabbit. It belongs to the lagovirus genus in the Callissaveridae family of viruses. It is a non enveloped, icosahedral, single stranded positive sense RNA virus. The virus capsid is comprised of ninety dimers of a single capsid subunit VP sixty protein. The VP sixty protein has three domains, an N terminal arm the NTA a shell s that forms a scaffold which protects the viral RNA, and a flexible protruding domain P at the capsid surface, which contain the determinants for virus host receptor interactions and antigenic diversity. The P domain can be further divided into P one and P two subdomains, and the P two

14:58 subdomain is located at the outermost surface exposed region of the viral capsid. In two thousand and ten, a new RHDV related virus with a distinctive pathogenic profile was found in France. This virus is known as RHDV two or rhdvb, and it has rapidly spread throughout domestic and wild rabbit populations in Italy, Spain, Portugal, Germany, the United Kingdom, and the Azores. There are several non pathogenic Callisa viruses that are genetically related, but they're also relatively distant from RHDV. The mortality rate of RHDV is anywhere between eighty to one hundred percent. Rabbits are not susceptible to the virus from birth. They become more susceptible as they get older. Susceptibility begins around five or six weeks and steadily increases to the eighth or ninth week of life when they are fully susceptible.

16:04 This virus can live for weeks outside of the host and is spread very easily by the fecal, oral, nasal, conjunctival, and parental routes. Animals who come to graze where infected animals have been grazing will generally get the disease. It is also spread by vectors such as fleas flies and mosquitoes. Because the virus is resistant to environmental inactivation, fomites are important in the spread of the disease. It also survives for long periods in infected carcasses. Domestic rabbits can get it from hutches where infected rabbits have previously been housed, and most disinfectants won't even touch it. There are three clinical syndromes seen in RHDV.

16:55 The paracute form is characterized by sudden death with no clinical symp The acute form is characterized by anorexia and depression, followed by neurological signs respiratory distress, ocular hemorrhage and epistaxis, lymphopenia, and abnormalities and coagulation are also present in these animals. In the subacute form, similar signs may be present, but they're considerably milder and most of these rabbits will survive. Hepatic necrosis is consistent through the animals that die, and most experienced disseminated intravascular coagulopathy and thrombosis. One study found that liver cell death is induced upon infection and is due to apoptosis.

17:47 This program cell death mainly affects hypotocytes, but macrophages and endothelial cells have also presented hallmarks of apoptosis. Hypotocyte apoptosis produced extensive parenchymal destruction that caused the lethal, acute fulminant hepatitis that is so characteristic of the disease. It's postulated that apoptosis and RhD may be the determining factor in the development of d C. Let's take a minute to hear from our sponsors, then I'll be back to talk about the history of the disease. Are you a true crime advocate? Are you passionate about uncovering the truth and bringing justice to victims? Do you love the paranormal and spooky tales? Then you don't want to miss the True Crime and Paranormal Podcast Festival in Austin, Texas. It'll be going on from August twenty fifth to the twenty seventh in twenty twenty three. This festival features panel discussions, workshops, live podcasts, all focusing on ethics and advocacy in the true crime sphere. Get your tickets now at www dot Truecrime Podcast Festival dot com and join us in Austin for an unforgettable experience. Don't miss out on the chance to connect with other advocates and take your passion for truecrime and paranormal to the next level. Use Code Consequences at checkout for fifteen percent

19:19 off the ticket price. That's Truecrime Podcast Festival dot com with promo Code Consequences at checkout for fifteen percent off the ticket price. Special guests will include Julie Murray, Terranewell, and Call your Landry to name a few. I'll be there representing another podcast that I'm involved with, True Consequences. Come by and meet Eric Carter Landin and I We would love to meet you. Our HD was first reported in China in nineteen eighty four in the Jane Shue province after a group of commercially bread and gorah rabbits had been imported from Germany. It's thought that the disease may have started in Germany and been imported to China, but there were never any reports of RhD before nineteen eighty four, so it's a chicken and egg story. No one really knows which came first. However, in less than a year, the virus had killed one hundred and forty million domestic rabbits in China and had spread over an area of fifty thousand square kilometers. Korea was the next country to report the disease after importing rabbit fur from China. Italy saw its first outbreak in nineteen eighty six. Then it spread to the rest of Europe and became endemic in several countries. European rabbits

20:53 originated in the Iberian Peninsula and they are a key species in the ecosystem, but after the first outbreaks in Spain and Portugal in nineteen eighty eight and nineteen eighty nine, respectively, there was a severe reduction in wild populations. North Africa began to experience RhD outbreaks and domestic populations around the same time. In nineteen eighty eight, Mexico became the first country in the Americas to undergo an outbreak of RhD after importing rabbit products from China. Mexico is the only country to have somehow eradicated the disease, though the last outbreak there occurred in nineteen ninety two. It's worth noting that the successful eradication may have been due to the absence of natural populations of wild European rabbits in that country. North America wouldn't report an outbreak until two thousand and it has only reported a few outbreaks since the US RhD is considered a foreign disease and it is reportable to the USDA should an outbreak occur. The virus finally made its way to distant regions and was eventually reported in Cuba, Uruguay, and Reunion Island. In Australia and New Zealand, where rabbits are considered to be agricultural pests and major threats

22:25 to the endemic wildlife, flora and fauna, RhD was considered an agent for rabbit control. These countries used biological warfare against rabbit populations. If you have a subscription to the show you'll get to hear the episode on the House that Jack built. That episode explains what happens when feral species are introduced into an area and how they take over. It also addresses the efforts that governments and locals make to get rid of those populations. It's a good episode. If you haven't subscribed, you should okay shameless plug over. Research efforts began in New Zealand and Australia to harness a strain of the disease and use it as biocontrol against rabbits. In nineteen ninety one, r HDV check Reference strain was used to assess the efficacy and host specificity of the disease. After the Australian authorities approved the use of the strain, it was released in the Wardang Island in Spencer Gulf, South Australia. Despite strict quarantine measures, the virus made its way to the mainland in nineteen ninety five. Possibly it was carried by insects or maybe the wind. In less than two years, it had become endemic across Southern Australia at a rate of fifty kilometers per week. Areas experienced

24:00 a ninety five percent reduction in rabbit populations, particularly in the more arid climates. After careful consideration of the pros and cons of introducing RDHV to the country, New Zealand decided against it. That didn't stop local landowners from illegally introducing the virus to the country, though, after studying the carcasses of dead animals, the strain looked a whole lot like the check strain that had been introduced to Australia. This gave rise to the suspicion that the virus could have been illegally imported from Australia. One of the challenges in identifying and naming the virus came from the fact that it can't be grown in culture. Researchers suspected several different viruses, picornovirus, parvovirus, and parvo like virus. It was finally assessed in nineteen ninety as a member of the calisa Veridae family. The first complete genome sequence was obtained in nineteen ninety one, and this revealed that RHDV was very similar to other callissa Veridae viruses that were nonpathogenic, But it wasn't until nineteen ninety seven that the first phylogenic analysis of RHDV isolates using different locations and spanning the years from nineteen eighty seven to nineteen ninety five was performed.

25:30 All the available information was included in the study and this led to the identification of three major branches and supported a high degree of homology between samples. It also showed that there were clusters of RHDV strains that correlated closer with the year of isolation, rather than the areas that they were collected from. Lagal and his team found this same pattern among French isolates and further assigned the isolates into three chronologically established geno groups G one, G two, and G three. It was later found that France G one and G two had disappeared and three new subgroups had appeared. G four had mutated from G three. G five and G six were both independent subgroups. G six corresponded to the first antigenic variant of RHDV, which had been previously detective by Capucci and his team.

26:37 This has since been designated as RhD V. A vaccine research soon began and by using monoclonal antibody one H eight, protection could be conferred to experimentally infected rabbits. So There is a vaccine against RHDVA, which is the most common type of RHDV. But as we know, viruses mutate to evade host immunity, and it's no different with RhD RHDVB is resistant to the current vaccines and so it can evade prophylactic measures. The realization that it kills quickly and without warning makes it much harder to control. That said, passive immunity can work in an emergency. Inoculation is achieved by using hyperimmune anti serum from rabbits who exhibit very mild symptoms or are asymptomatic. This is not a long term solution though, As I've discussed in the past, herd immunity can only be attained by vaccination. There is no therapy in place for animals with RHDV. Prevention and control are the best bets when it comes to animal survival. If they don't get it, they can't die from it. Since there is still no way to culture this virus, vaccines are produced from the tissue suspensions of experimentally

28:11 infected rabbits, then the virus is inactivated. Research is ongoing to find a safer vaccine using recombinant DNA where the VP sixty protein is produced in E. Coli, insect cultured cells, yeast plants, insect larvae, and recombinant animal derived viruses. Most of these experiments have been successful, but proper disposal of unused vaccine and dirty needles is concerning. While the vaccines are using recombinants and inactivated virus proteins, there is no guarantee that without proper disposal in place, that virus couldn't find another host and become pathogenic. Vaccination and biocontainment are possible in commercial rabbit trees, but none of this is practical when we're talking about wild rabbits. The stress of catching these animals alone may increase mortality, and since the immunity from the vaccines wanes in a year, the treatment would have to be performed again and again as we speak. Researchers are exploring vaccine delivery systems that would be more logistically sound in wild populations. If the vaccine could be spread over large swaths of land where the rabbits could either ingest them or breathe them in, that would be the perfect solution, but then we still have the problem of the vaccine being unstable. Though I didn't run onto anything,

29:44 indicating that they were ongoing studies with mRNA That would be the best solution to the problem. Research is currently being done using RHDV as a cancer and pathogen treatment in humans. Using genetic engineering, r hdv VLP have been shown to efficiently incorporate antigens that might present to immune cells and to elicit an adequate cell mediated and humoral immune response. If this works, it could be easily reproduced. It would be very inexpensive, and since it's coming from a non human virus, they're not susceptible to pre existing neutralizing antibodies. Rabbits are an important part of the ecosystems that they inhabit. Without them, many prey animals wouldn't survive. This disease could kill off a necessary food source for coyotes, hawks, eagles, bears, and other prey animals. Then we have to wonder if this virus will jump. It hasn't yet, but it's a fairly fast mutator, so it could. That would be disastrous for any animal that depends on the rabbit as a food source, including people. Okay, that's rabbit hammorrhagic disease. Scary stuff. There was a tweet directed at me from

31:15 my friend Anne at Unsolved Virginia. Apparently several cases of Powassan virus have been found in Maine this year. This is a nasty virus that causes encephalopathy, and well, there's no vaccine nor treatment. Ticks seem to be everywhere, so they're hard to avoid. Dat is a double edged sword. It works to keep the blood suckers away, but the long term may be questionable. Powassan virus is carried by ticks and is a rare disease that occurs mostly in the northeast US, Canada and eastern Russia. I'll be talking a lot about vector borne diseases in a future season. Maybe will tune that up for season eight. All I can say is that the coming plague isn't going to be vector born. It's going to be something that's passed as easily as the common cold. Thanks for giving me the heads up on pouassan, and so many of you contacted me this time. I really appreciate all of you emailing, facebooking, tweeting, and well those who know me are texting and calling.

32:28 So I'm grateful for all of you. If you would like to contact me. Please feel free to reach out to me on the socials, or you can drop me a line at Jackie at cause of death one hundred secs dot net. You can also leave a message on my website at www. Cause of Death one hundred secs dot net. Take a look at the show notes where you'll find this month's sponsor. I do love True Leaf Market. Arted seeds for twenty four different plants and every single one of them has sprouted. They look great now. If I can leave them until the third leaf then replant, I'll be fine. Really, go check out true Leaf Market.

33:15 I have never been so successful. Head on over to the Patreon page and sign up for ad free content, bonus content, and other goodies. You can also subscribe on Apple Subscriptions for ad free and bonus content. Don't forget to rate, review and subscribe on your favorite podcast platform. Those charts really do mean a lot, and every download, every subscription, every review, and every share counts. Thank you all again, and I'll see you in two weeks when I'll be talking about bats disease and the environment. Until then, get out and enjoy the outdoors, but avoid the those vectors.