WEBVTT - Ep 91 Myxomatosis: Down the rabbit hole 0:00:02.120 --> 0:00:04.680 No one would believe the mischief the rabbits are doing 0:00:04.760 --> 0:00:07.440 unless they could see it. The sheep farmers have not 0:00:07.520 --> 0:00:10.080 tried to clear them, and now many of the runs 0:00:10.119 --> 0:00:12.200 are so bare that there is not grass enough to 0:00:12.240 --> 0:00:15.640 feed the rabbits, let alone the sheep. The consequence is 0:00:15.680 --> 0:00:18.760 that the rabbits are traveling in thousands in search of food. 0:00:19.320 --> 0:00:22.480 Last Friday morning, soon after sunrise, I met a swarm 0:00:22.600 --> 0:00:25.439 coming from the hills. I never saw such a thing before. 0:00:25.880 --> 0:00:28.200 The ground was scarcely to be seen for about a 0:00:28.280 --> 0:00:31.640 mile in length. Five weeks since I could not find 0:00:31.680 --> 0:00:34.000 a rabbit on my land, but since then we have 0:00:34.120 --> 0:00:37.159 killed thousands. When the sun is hot, you can go 0:00:37.240 --> 0:00:39.440 along the fences or any place where it is shady 0:00:39.440 --> 0:00:40.800 and kill hundreds. 0:00:40.360 --> 0:00:40.920 With a stick. 0:00:41.560 --> 0:00:44.400 Today has been cool, but still I several times killed 0:00:44.400 --> 0:00:47.000 two or three at a blow. The paddocks stink with 0:00:47.040 --> 0:00:47.720 the dead ones. 0:00:48.960 --> 0:00:53.000 Immediately prior to the liberation of Mixamatosis, a combination of 0:00:53.000 --> 0:00:55.600 circumstances had led to the build up of rabbits to 0:00:55.920 --> 0:00:58.840 very high levels over much of most of their range, 0:00:59.280 --> 0:01:02.440 and the situation in many areas could only be described 0:01:02.520 --> 0:01:08.080 as desperate. The change has been almost miraculous. The landscape 0:01:08.120 --> 0:01:12.120 in some areas has been virtually transfigured. Hills that had 0:01:12.160 --> 0:01:15.320 been grazed to the soil for decades and whose slopes 0:01:15.360 --> 0:01:18.640 appeared gray and red on the horizon are now clothed 0:01:18.680 --> 0:01:22.480 in grass. The broad margins of the country roads lying 0:01:22.520 --> 0:01:26.160 outside the boundary fences of grazing properties tended to carry 0:01:26.200 --> 0:01:29.679 dense rabbit populations, and as often as not, showed it 0:01:29.720 --> 0:01:32.920 in the poverty of their groundcover. It is now usual 0:01:32.959 --> 0:01:36.280 to see tall grass to the road's edge looking over 0:01:36.319 --> 0:01:38.560 the fences. It is now very rare to see a 0:01:38.560 --> 0:02:18.440 paddock without a dense and healthy pasture. 0:02:27.720 --> 0:02:30.320 Wow, I love it. 0:02:30.400 --> 0:02:33.600 And those two passages just got me so excited for 0:02:33.680 --> 0:02:34.240 this episode. 0:02:35.040 --> 0:02:39.280 It's very interesting to kind of see like very clear 0:02:39.360 --> 0:02:45.760 before and after quotes. Yeah, those those two quotes I 0:02:45.880 --> 0:02:50.399 lifted from a book called The Biological Control of Vertebrate Pests, 0:02:51.000 --> 0:02:54.239 and they are both about the topic of today's episode. 0:02:56.080 --> 0:03:02.040 Make Sematosis. Make Sematosis the Radiohead song. So we're gonna 0:03:02.080 --> 0:03:04.680 talk in this episode all about Tom Yorke and what 0:03:04.760 --> 0:03:07.200 inspired him to write the song mix and Metosis. 0:03:07.840 --> 0:03:09.680 I have no idea what you're talking about. 0:03:10.480 --> 0:03:15.840 Aaron Okay. Miximatosis is actually the topic of today's episode. 0:03:15.880 --> 0:03:20.480 But it's a virus that affects rabbits, and it also 0:03:20.560 --> 0:03:23.440 happens to be the title of a Radiohead song. 0:03:23.840 --> 0:03:26.320 Wow, I definitely did not know that last part. 0:03:29.280 --> 0:03:32.680 I listened to it in prep uh for the recording today. 0:03:32.919 --> 0:03:34.920 Nice, we should try and get the rights. 0:03:34.840 --> 0:03:41.960 You know, Bloodmobile? Can you write us a knockoff? I 0:03:41.960 --> 0:03:46.160 feel like I should introduce myself before we begin. The 0:03:46.200 --> 0:03:50.400 rest of this introduction is always the place. Hi, I'm 0:03:50.480 --> 0:03:51.440 erin Welsh. 0:03:51.160 --> 0:03:53.120 And I'm Aaron Aman Upnike. 0:03:53.000 --> 0:03:55.200 And this is this podcast will kill you. 0:03:55.440 --> 0:03:57.680 Yes, it is welcome if this is your first time here. 0:03:57.720 --> 0:04:00.000 We usually do things in a different order. 0:04:00.080 --> 0:04:02.160 And maybe a little bit more clean and a little 0:04:02.200 --> 0:04:03.600 bit more organized. 0:04:04.040 --> 0:04:06.840 We're just so excited about mix and metosis. And I 0:04:06.840 --> 0:04:09.200 think you were really excited to tell me about Radiohead. 0:04:09.400 --> 0:04:11.000 I really was, I really was. 0:04:11.520 --> 0:04:13.360 Did you know that I wasn't going to know? I 0:04:13.400 --> 0:04:15.840 feel like you did. I. 0:04:15.840 --> 0:04:28.280 I gave it about a fifty five to forty five Okay, okay, yeah. 0:04:23.800 --> 0:04:26.839 But yes, a rabbit viral disease is what we're talking 0:04:26.839 --> 0:04:28.919 about today. It's going to be great, even if you 0:04:28.960 --> 0:04:32.359 think you don't like animal viruses, or you don't like rabbits, 0:04:32.520 --> 0:04:35.240 or you do like rabbits, you're gonna love this episode. 0:04:35.400 --> 0:04:38.560 I think so too. This is like if you just 0:04:38.600 --> 0:04:41.440 clicked on this out of sheer curiosity and you're like, Okay, 0:04:41.520 --> 0:04:44.520 now I'm having my doubts. This is a rabbit disease. Yeah, 0:04:44.640 --> 0:04:47.920 I promise. I think this is one of the most 0:04:48.440 --> 0:04:53.919 interesting and important stories about disease that we have covered 0:04:53.920 --> 0:04:57.520 on this podcast because it covers so many different topics, 0:04:57.520 --> 0:04:58.880 so many different concepts. 0:04:59.200 --> 0:05:02.799 Yeah it is. It is such a good story. Promise 0:05:03.200 --> 0:05:03.520 it is. 0:05:05.440 --> 0:05:07.120 But we have some business to take care of. 0:05:07.440 --> 0:05:08.000 We do. 0:05:08.360 --> 0:05:10.520 It is first quarantiny time. 0:05:10.800 --> 0:05:13.240 It is What are we drinking this week? 0:05:13.360 --> 0:05:16.880 We're drinking Bunny's Bug? Get it. 0:05:19.800 --> 0:05:25.560 Bunny's Bug is a tasty little drink that has hop water. 0:05:25.480 --> 0:05:27.760 Because because bunnies hop. 0:05:28.040 --> 0:05:30.200 I don't know if we needed to explain that, but I. 0:05:30.200 --> 0:05:31.760 Like it though, I like the explanation. 0:05:33.279 --> 0:05:38.120 It has lime juice, it has mescal, it has simple syrup, 0:05:38.360 --> 0:05:40.120 and it has some grapefruit juice. 0:05:40.600 --> 0:05:41.760 Yum delish. 0:05:41.960 --> 0:05:44.920 We'll post the full recipe for that quarantini as well 0:05:44.920 --> 0:05:48.080 as our non alcoholic plusy Berta on our website, This 0:05:48.080 --> 0:05:50.560 podcast will kill You dot com and all of our 0:05:50.560 --> 0:05:51.760 social media channels. 0:05:52.120 --> 0:05:54.680 Oh is it my turn to do the website information now? 0:05:54.920 --> 0:05:55.599 Okay, it is. 0:05:56.279 --> 0:06:01.400 On our website. You can find transcript You can find 0:06:01.640 --> 0:06:04.280 our bookshop dot org affiliate account. You can find our 0:06:04.279 --> 0:06:08.160 good Reads list. You can find links to music by Bloodmobile. 0:06:08.720 --> 0:06:12.200 You can find all of the sources for each one 0:06:12.240 --> 0:06:15.120 of our episodes. You can find links to the promo 0:06:15.200 --> 0:06:18.400 codes that we mentioned in our ads, merch. 0:06:18.720 --> 0:06:21.919 We've got transcripts, We've got. 0:06:22.200 --> 0:06:23.040 Yeah, we got it all. 0:06:23.080 --> 0:06:24.480 That's got to be it. 0:06:25.040 --> 0:06:31.760 Yeah, okay, well then should we you know, let's get 0:06:31.800 --> 0:06:32.159 into it. 0:06:32.320 --> 0:06:34.839 Let's do it. Okay, we've hyped it enough, you think, 0:06:35.040 --> 0:06:36.359 I hope we haven't overhyped it. 0:06:36.680 --> 0:06:39.080 Oh, let's find out. 0:06:39.800 --> 0:06:50.679 Right after this break. 0:07:04.480 --> 0:07:09.080 Fair warning, listeners, I am starting off this biology section 0:07:09.279 --> 0:07:12.239 kind of intentionally withholding. 0:07:11.680 --> 0:07:18.160 Details for later dramatic effect. So let us begin. 0:07:19.080 --> 0:07:25.120 Mixamatosis is a disease caused by the Mixoma virus, which 0:07:25.160 --> 0:07:27.560 is a member of a family we are familiar with 0:07:27.640 --> 0:07:30.720 here on the podcast. It is a pox virus, as 0:07:30.760 --> 0:07:34.280 in smallpox. I don't think we've covered any other pox viruses. 0:07:34.400 --> 0:07:42.160 I was just gonna ask I can't remember. Oops, But anyways, Yeah, 0:07:42.200 --> 0:07:45.520 this is a different genus of poxvirus. This is a 0:07:45.640 --> 0:07:51.680 lay poroxy pox virus, and smallpoxes an orthopox pox virus 0:07:51.720 --> 0:07:52.520 if anyone cares. 0:07:52.880 --> 0:07:55.080 But all of the pox viruses are. 0:07:54.960 --> 0:07:58.960 Double stranded DNA viruses. They have pretty big genomes. And 0:07:59.000 --> 0:08:01.920 the virus itself, if you look at it under a microscope, 0:08:02.000 --> 0:08:04.240 is shaped like a brick, which I just think is 0:08:04.280 --> 0:08:06.640 funny that every single paper described it as. 0:08:06.480 --> 0:08:07.760 A brick shaped virus. 0:08:07.920 --> 0:08:12.120 Interesting it is, huh the poxvirus. 0:08:12.120 --> 0:08:18.000 Mixoma virus replicates in the cytoplasm of cells, and it's 0:08:18.040 --> 0:08:21.360 a really fascinating virus because it has a lot of 0:08:21.400 --> 0:08:26.000 proteins that interact with the host immune response. That become 0:08:26.120 --> 0:08:29.160 really important in terms of how much disease we actually 0:08:29.240 --> 0:08:35.760 see in its various hosts, and Mixoma virus causes disease. 0:08:35.720 --> 0:08:36.840 Only in rabbits. 0:08:37.720 --> 0:08:42.800 It infects a large number of species of rabbits, but 0:08:42.880 --> 0:08:45.280 as far as I can tell, it doesn't cause clinical 0:08:45.280 --> 0:08:47.800 disease in any of the other hosts that it has 0:08:47.880 --> 0:08:51.200 been tested in other than rabbits. And I think one 0:08:51.280 --> 0:08:55.560 species of hair yeah, which are all called lagomorphs. I 0:08:55.600 --> 0:09:02.600 learned so many new words researching this episode. But Mixima virus, interestingly, 0:09:02.880 --> 0:09:06.000 can replicate in vitro like in a petri dish or 0:09:06.040 --> 0:09:09.920 a cell culture bottle, in cells from many many different 0:09:09.960 --> 0:09:15.000 host species, including human cancer cells, which it turns out 0:09:15.080 --> 0:09:18.640 are particularly good at letting mixoma virus in and letting 0:09:18.679 --> 0:09:19.319 it replicate. 0:09:19.840 --> 0:09:20.400 Interesting. 0:09:21.080 --> 0:09:23.720 Very And I'm throwing that little tidbit out there and 0:09:23.760 --> 0:09:26.600 then just gonna leave it to dangle and circle back 0:09:26.640 --> 0:09:27.120 to it at. 0:09:27.000 --> 0:09:28.360 The very end of the episode. 0:09:28.480 --> 0:09:31.120 Okay, I was, I was all poised to ask a question, 0:09:31.160 --> 0:09:33.720 but I can tell you're strange. 0:09:34.080 --> 0:09:38.000 Okay, but today we're talking about rabbits. So this Mixoma 0:09:38.080 --> 0:09:42.640 virus causes the disease known as miximatosis in rabbits and hairs, 0:09:42.679 --> 0:09:46.120 and specifically, it causes the severe disease that we know 0:09:46.240 --> 0:09:51.360 of as miximatosis in the European rabbit Uricdologus cuniculus. If 0:09:51.400 --> 0:09:52.400 I'm saying that right. 0:09:52.400 --> 0:09:57.000 Do you remember the Book'spinicula. No, it was like about 0:09:57.000 --> 0:10:02.280 a vampiric rabbit that sucked the juices out of vegetables. 0:10:04.840 --> 0:10:06.959 I do not. I've never read that book. 0:10:07.120 --> 0:10:09.720 Really, it was like a series of books for kids. 0:10:10.040 --> 0:10:13.360 But I remember, like when I saw the scientific name 0:10:13.400 --> 0:10:16.160 of the European rabbit, I was like, Oh my gosh, 0:10:16.200 --> 0:10:18.360 that's where the that it comes from. 0:10:20.320 --> 0:10:23.640 That's very funny. I have not read those books. I'll 0:10:23.640 --> 0:10:24.880 put them on my Goodreads lists. 0:10:24.960 --> 0:10:25.679 They're wonderful. 0:10:26.600 --> 0:10:28.960 Okay, so let's go over what this disease looks like 0:10:29.280 --> 0:10:33.160 in this European rabbit. So the incubation period tends to 0:10:33.200 --> 0:10:37.480 be about four days and the initial symptoms. I'll kind 0:10:37.520 --> 0:10:39.880 of go over what this progression of disease looks like 0:10:40.760 --> 0:10:44.960 initially after that, about four days after infection, the symptoms 0:10:45.000 --> 0:10:47.800 are generally redness in the eyes, so kind of a 0:10:47.880 --> 0:10:54.559 conjunctival inflammation, and an elevated body temperature. What temperature are 0:10:54.840 --> 0:10:56.319 rabbits bodies normally, you. 0:10:56.280 --> 0:10:59.360 May ask, I would ask, yes, yeah, well I did 0:10:59.400 --> 0:11:00.679 google it. 0:11:00.679 --> 0:11:02.880 It's about one o two to one oh three fahrenheit, 0:11:02.880 --> 0:11:04.800 which is thirty eight point nine to thirty nine point 0:11:04.800 --> 0:11:07.920 four c. So they run a little hot. This virus 0:11:07.960 --> 0:11:12.040 makes them a little hotter. And then following after a 0:11:12.080 --> 0:11:16.400 few more days after initial infection, after these kind of 0:11:16.520 --> 0:11:22.520 red eye symptoms, these secondary lesions appear. They're often called 0:11:22.720 --> 0:11:28.960 cutaneous popular lesions. Basically just little lumps, little skin colored 0:11:29.080 --> 0:11:33.640 lumps on the rabbits that appear kind of throughout their body, 0:11:33.679 --> 0:11:37.959 but most prominently at the bases of their ears. They 0:11:38.000 --> 0:11:43.440 also get swelling in the anogenital region almost universally, and 0:11:43.480 --> 0:11:46.040 then they begin to have discharge, both kind of a 0:11:46.120 --> 0:11:51.000 clear like cirrus discharge as well as a mucopurulent or 0:11:51.080 --> 0:11:55.079 kind of pus filled discharge from the nose and the eyes. 0:11:56.240 --> 0:11:59.320 And then by days eight to ten, these poor little 0:11:59.360 --> 0:12:03.480 rabbits will have a very very swollen face, droopy ears 0:12:03.559 --> 0:12:05.880 because of all the swelling at the base of their ears. 0:12:06.520 --> 0:12:10.560 They'll have severely swollen eyelids and really goopy eyes, goopy 0:12:10.600 --> 0:12:13.720 noses that get so filled with gunk that their tiny 0:12:13.720 --> 0:12:18.040 little nasal passages get clogged, and then all across their body, 0:12:18.080 --> 0:12:21.480 like throughout their body, they'll have these little anywhere from 0:12:21.600 --> 0:12:25.600 a few millimeters to a few centimeters these little skin 0:12:25.840 --> 0:12:30.319 swellings across their body, and their anogenital region will become 0:12:30.400 --> 0:12:35.960 really really swollen, especially the testicles, and then their breathing 0:12:36.240 --> 0:12:39.920 will become more difficult and labored. They'll have this kind 0:12:39.920 --> 0:12:45.280 of stirter, which is that like gasping inhale. And they 0:12:45.320 --> 0:12:48.400 generally die between eight to twelve days following infection. 0:12:48.640 --> 0:12:51.280 And so that's like eight to twelve days after they 0:12:51.320 --> 0:12:54.640 first get exposed, so it's only like a period of four. 0:12:54.520 --> 0:12:58.360 To yeah, four to six days, wow, four. 0:12:58.200 --> 0:12:58.760 To eight days. 0:12:58.840 --> 0:13:04.839 Yeah, it's a very very rapid course of disease. And mixamatosis, 0:13:05.360 --> 0:13:11.040 this disease classically has an almost unbelievably high mortality rate 0:13:11.600 --> 0:13:15.000 in the European rabbit ninety nine point eight to one 0:13:15.120 --> 0:13:19.160 hundred percent mortality. This is along the lines of I 0:13:19.160 --> 0:13:23.079 think just rabies and preons are the only two diseases 0:13:23.160 --> 0:13:25.520 that match this kind of mortality that we've ever covered. 0:13:26.080 --> 0:13:28.520 Yeah, we yeah, that we've covered so far. 0:13:29.000 --> 0:13:31.960 Yeah. Yeah. 0:13:32.240 --> 0:13:35.920 And so the virus, this mixoma virus is present in 0:13:36.040 --> 0:13:39.480 all of those goopy secretions as well as in all 0:13:39.559 --> 0:13:43.560 of those skin lesions, and it's very easily transmitted to 0:13:43.640 --> 0:13:50.120 other rabbits, potentially by direct contact, but mostly by various 0:13:50.280 --> 0:13:54.800 biting arthropod vectors. But even though this is a virus 0:13:54.800 --> 0:13:59.679 that's transmitted by vectors like mosquitoes and lice or fleas, 0:14:00.800 --> 0:14:05.239 and especially in terms of epizootics or these outbreak scenarios. 0:14:05.280 --> 0:14:09.319 It does seem like vectors, especially mosquitoes, are pretty pivotal 0:14:09.440 --> 0:14:13.920 in terms of large scale transmission. Without them, these outbreaks 0:14:13.960 --> 0:14:17.280 don't really spread or don't spread us quickly. Oh yeah, 0:14:17.600 --> 0:14:22.400 but the virus does not rely on mosquitos for its 0:14:22.440 --> 0:14:27.760 life cycle or transmission. It doesn't infect or replicate in 0:14:27.880 --> 0:14:32.000 mosquitoes the way of most, if not, I think all 0:14:32.160 --> 0:14:34.640 of the vector born diseases that we've ever covered on 0:14:34.680 --> 0:14:39.280 this podcast do. What that means is that this vectoral 0:14:39.320 --> 0:14:45.040 transmission is just mechanical, right, which means that the virus 0:14:45.080 --> 0:14:48.720 has to be in very very high tighters in the 0:14:49.000 --> 0:14:53.960 cutaneous lesions, these skin lumps on the rabbits in order 0:14:54.080 --> 0:14:57.040 for the mosquito or the flea to have enough virus 0:14:57.120 --> 0:14:59.520 on its mouth parts to then transmit it to the 0:14:59.560 --> 0:15:00.720 next rabbit. 0:15:01.280 --> 0:15:01.840 Yeah. 0:15:02.040 --> 0:15:06.560 Do you know what the infectious doses like in rabbits? 0:15:06.640 --> 0:15:06.880 Yeah? 0:15:07.240 --> 0:15:09.720 I don't know exactly, but I do know that it 0:15:09.840 --> 0:15:13.880 seems like critical levels in the skin tissue are like 0:15:14.000 --> 0:15:18.640 ten to the seventh viral particles per gram of rabbit tissue, 0:15:19.000 --> 0:15:21.920 So that's like a little over ten million or so 0:15:22.400 --> 0:15:25.360 viral particles per gram, so really really high tighters are 0:15:25.440 --> 0:15:27.960 necessary for this to be efficiently transmitted. 0:15:28.040 --> 0:15:31.840 Okay, yeah, and I'm assuming also that the mosquito has 0:15:31.880 --> 0:15:35.640 to bite one of the lesions or like pick up 0:15:35.720 --> 0:15:36.920 and where the gunk. 0:15:36.720 --> 0:15:39.800 Is exactly yes, And that is why it's thought that 0:15:39.960 --> 0:15:43.920 especially those base of the ear swellings might be very 0:15:43.960 --> 0:15:47.480 important for viral transmission, because that's a commonplace for mosquitoes 0:15:47.560 --> 0:15:53.119 and other vectors to bite the rabbits. So, now, anyone 0:15:53.560 --> 0:15:57.760 who's listening who knows the story of mix andmatosis knows 0:15:57.760 --> 0:16:01.000 that that description that I just gave of this horrifying 0:16:01.240 --> 0:16:05.920 lethal disease of the European rabbit is not the whole story. 0:16:07.400 --> 0:16:12.040 So let me dive a little bit deeper. So, first off, 0:16:12.560 --> 0:16:18.000 Mixoma virus is still and was first a virus of 0:16:18.040 --> 0:16:23.480 a different rabbit species, entirely many different rabbit species, specifically 0:16:23.720 --> 0:16:28.640 the Silvie Lagis species rabbits endemic to South and North 0:16:28.680 --> 0:16:31.479 America and in the Americas. 0:16:31.720 --> 0:16:33.760 In these species of rabbits. 0:16:33.680 --> 0:16:38.040 Mixoma virus causes an entirely different disease, if you can 0:16:38.120 --> 0:16:42.000 even call it a disease, really, in American rabbits of 0:16:42.040 --> 0:16:47.040 the genus silvie lagis mixomavirus causes a single skin lump, 0:16:47.120 --> 0:16:50.160 a single mixoma and that's it. 0:16:50.760 --> 0:16:52.160 That's it, that's what it causes. 0:16:52.320 --> 0:16:56.359 At the sight of inoculation, you get one big cutaneous 0:16:56.480 --> 0:16:59.920 lump and that's it. So right off the bat here, 0:17:00.200 --> 0:17:01.200 this virus. 0:17:00.880 --> 0:17:02.280 Is getting interesting. 0:17:01.960 --> 0:17:06.600 Because we see this huge variation in disease between host 0:17:06.640 --> 0:17:11.080 species in terms of the pathogenicity of this same virus. 0:17:12.040 --> 0:17:13.639 So that's the first part of this story. 0:17:14.800 --> 0:17:16.879 But number two is what I know You're going to 0:17:16.960 --> 0:17:20.040 talk a lot more about aarin in the history section, 0:17:21.119 --> 0:17:25.000 but that is that Mixoma virus is virulence in the 0:17:25.080 --> 0:17:31.560 European rabbit dramatically changed over time, so this incredibly lethal 0:17:31.720 --> 0:17:36.560 version is not the only one which exists. And Okay, 0:17:36.640 --> 0:17:38.360 I don't want to step on your toes too much 0:17:38.400 --> 0:17:41.920 because I think that hearing this story in its entirety 0:17:42.040 --> 0:17:44.199 for the first time for most of our listeners is 0:17:44.240 --> 0:17:47.400 going to be so good. So at this point, let 0:17:47.440 --> 0:17:50.960 me ask you Erin, do you have any other questions 0:17:50.960 --> 0:17:53.359 about the transmission or details that you want to know 0:17:53.560 --> 0:17:55.840 about the path of physiology of this virus. 0:17:56.280 --> 0:18:01.400 Yes, okay, okay, So in the europe rabbit and these 0:18:01.520 --> 0:18:05.480 American rabbits, does the virus sort of enter in the 0:18:05.520 --> 0:18:09.480 same way and go through its normal replication cycle and 0:18:09.920 --> 0:18:12.960 move to the different parts of the skin or ears 0:18:13.119 --> 0:18:16.399 or whatever the body to replicate and cause lesions in 0:18:16.440 --> 0:18:18.800 the same way over the same time period. Where do 0:18:18.920 --> 0:18:20.320 the differences start to jump in? 0:18:21.160 --> 0:18:21.919 Great question? 0:18:22.119 --> 0:18:25.920 Okay, So this mixamma virus when it gets inoculated under 0:18:25.920 --> 0:18:29.040 the skin, either from a mosquito probe or a little 0:18:29.240 --> 0:18:33.760 flea mouth or a needle in a lab, the virus 0:18:33.800 --> 0:18:37.439 first infects the rabbits skin cells, their epidermal cells, or 0:18:37.440 --> 0:18:41.119 their dermal cells, and it quickly rises to pretty high 0:18:41.200 --> 0:18:44.439 tighters in those skin cells, in those lumps that appear. 0:18:45.880 --> 0:18:49.840 And then in addition to infecting the epidermal and dermal cells, 0:18:50.240 --> 0:18:53.920 this virus will go on to infect dendritic cells, which 0:18:53.960 --> 0:18:55.919 I think we've touched on a number of times on 0:18:55.960 --> 0:18:58.320 this podcast. But these are white blood cells that hang 0:18:58.359 --> 0:19:01.560 out in our skin and from there spread to our 0:19:01.640 --> 0:19:05.360 lymphatic system, and their goal is to present to other 0:19:05.400 --> 0:19:08.240 white blood cells these viral particles so that we can 0:19:08.240 --> 0:19:11.480 start to mount an immune response. But what happens with 0:19:11.600 --> 0:19:15.080 mixomavirus is it begins to replicate in these dendritic cells, 0:19:15.520 --> 0:19:19.080 and then when these dendritic cells spread to our lymph 0:19:19.119 --> 0:19:23.040 nodes or our bone marrow and our spleen, this virus 0:19:23.080 --> 0:19:26.160 is able to continue to replicate and infect other white 0:19:26.200 --> 0:19:30.960 blood cells. So this virus ends up being at very 0:19:31.040 --> 0:19:35.919 high concentrations in these skin lesions when they appear. And importantly, 0:19:36.040 --> 0:19:41.639 rabbits are not infectious until these skin lesions appear, but 0:19:42.160 --> 0:19:45.920 they also then have virus that spreads throughout their body, 0:19:46.200 --> 0:19:49.040 throughout their lymphatic system and is able to infect a 0:19:49.119 --> 0:19:52.919 number of different organs and potentially reach relatively high loads 0:19:52.920 --> 0:19:57.600 there as well. Now, to answer your question, Aaron, what's 0:19:57.600 --> 0:20:05.000 the difference between these different sentations the less virulent forms 0:20:05.040 --> 0:20:10.680 of maxoma virus and other similar laporoxypox viruses that are 0:20:10.760 --> 0:20:14.600 very closely related, some of which have been used to 0:20:14.640 --> 0:20:19.800 make vaccines against maxomavirus. One thing that they do differently 0:20:20.040 --> 0:20:23.679 is they're not as good at or in some cases, 0:20:23.720 --> 0:20:28.119 they can't at all infect those white blood cells. So 0:20:28.560 --> 0:20:33.280 what they cause is just a localized cutaneous infection causing 0:20:33.440 --> 0:20:38.920 localized cutaneous skin findings, but not causing systemic disease. Okay, 0:20:40.280 --> 0:20:42.919 and that seems to really make one big difference. So 0:20:42.960 --> 0:20:45.400 the virulence we know is at least in part related 0:20:45.600 --> 0:20:48.840 to how well this virus spreads beyond the epidermis and 0:20:48.920 --> 0:20:52.119 dermis and how well it invades and replicates within the 0:20:52.200 --> 0:20:54.919 lymphatic system and becomes a widespread infection. 0:20:55.840 --> 0:21:00.480 Gotcha. Okay, So then that kind of leads me into 0:21:00.920 --> 0:21:05.320 my next question, which is about immunity. So, as we'll 0:21:05.320 --> 0:21:08.720 talk about later on in this episode rabbits, the European 0:21:08.800 --> 0:21:13.919 rabbits that were exposed to mixematosis showed genetic resistance in 0:21:14.040 --> 0:21:17.399 later generations, and so they were able to be resistant 0:21:17.480 --> 0:21:23.640 to this virus separate, you know, from the virus's decreased virulence. 0:21:23.680 --> 0:21:25.200 That's a whole other part of the story or whatever. 0:21:25.359 --> 0:21:25.760 Yeah. 0:21:25.600 --> 0:21:29.080 Yeah, Basically these rabbits were able to resist getting infected. 0:21:29.480 --> 0:21:30.440 Yeah. 0:21:31.000 --> 0:21:35.480 Is the mechanism of resistance the same in the European 0:21:35.560 --> 0:21:38.520 rabbit as this sort of like, does it lead to 0:21:38.560 --> 0:21:43.159 the same reduced disease presence as we see in the 0:21:43.160 --> 0:21:44.080 American rabbits. 0:21:44.720 --> 0:21:49.080 Great questionnairein so the other part of the path of 0:21:49.080 --> 0:21:55.440 physiology of this virus is that mix omavirus mix oma 0:21:55.520 --> 0:21:59.720 viruses all of the different strains have a whole bunch, 0:22:00.160 --> 0:22:03.320 like more than I could possibly list in this podcast 0:22:03.880 --> 0:22:09.320 of proteins that regulate the host immune system in a 0:22:09.359 --> 0:22:13.760 way that facilitates infection. So they have these proteins that, 0:22:14.040 --> 0:22:20.240 for example, inhibit pro apoptotic molecules. What that means apoptosis 0:22:20.440 --> 0:22:23.439 is programmed cell death. That's one of the ways that 0:22:23.560 --> 0:22:28.399 animals immune systems have of targeting and fighting off viruses 0:22:28.440 --> 0:22:34.200 by identifying and killing virally infected cells. Right, while mixomavirus 0:22:34.240 --> 0:22:38.080 has a whole bunch of proteins that it creates specifically 0:22:38.119 --> 0:22:41.280 to prevent that process from happening in a number of 0:22:41.359 --> 0:22:45.760 different ways. They also have other proteins that help to 0:22:46.000 --> 0:22:50.520 interfere with the coordination and recruitment of leukocytes of white 0:22:50.560 --> 0:22:54.680 blood cells, basically down regulating that white blood cell response 0:22:54.760 --> 0:22:59.440 to infections. They have other proteins that block the presentation 0:22:59.680 --> 0:23:03.960 of anogens by those, for example, dendritic cells and other 0:23:04.080 --> 0:23:07.520 anigen presenting cells, so that they block these rabbits ability 0:23:07.600 --> 0:23:11.919 to make antibodies or even recognize the viral antigens. So 0:23:12.040 --> 0:23:15.159 Maxoma virus has a whole host of different mechanisms that 0:23:15.240 --> 0:23:18.879 affect a rabbit's immune response to infection that are really 0:23:18.920 --> 0:23:21.960 important in how much that rabbit is going to be 0:23:22.000 --> 0:23:25.320 able to resist or be susceptible to severe infection. 0:23:27.240 --> 0:23:29.680 So, to answer your questionarin. 0:23:30.600 --> 0:23:35.800 This, it seems like a lot of these specific proteins 0:23:35.880 --> 0:23:41.000 and mechanisms that the Maxoma virus has evolved in the 0:23:41.040 --> 0:23:45.560 American rabbits and are kind of perfectly suited in those 0:23:45.640 --> 0:23:47.880 rabbits to reduce the immune response to. 0:23:47.840 --> 0:23:49.640 A degree that allows for. 0:23:49.720 --> 0:23:55.320 The establishment of an infection but does not impair the 0:23:55.440 --> 0:24:00.320 rabbit's ability to survive and thrive, but also allows the 0:24:00.440 --> 0:24:03.560 establishment of an infection that's actually infectious, right, that has 0:24:03.640 --> 0:24:06.480 high enough tighters in the skin so that this virus 0:24:06.520 --> 0:24:07.440 can be transmitted. 0:24:08.000 --> 0:24:11.959 Okay, So it's like being able to tolerate and coexist 0:24:12.320 --> 0:24:14.520 exactly with Okay. 0:24:14.880 --> 0:24:18.760 Yeah, And so it's thought that then when those same 0:24:18.960 --> 0:24:23.879 kind of proteins were introduced to the European rabbit, like 0:24:24.119 --> 0:24:27.000 that is what allowed for this establishment of a very 0:24:27.000 --> 0:24:30.200 severe infection because of the difference in their immune response 0:24:30.240 --> 0:24:32.720 and how these proteins interacted with that immune response. 0:24:33.480 --> 0:24:34.600 And so, yes, that's one. 0:24:34.440 --> 0:24:36.480 Of the things that tends to change over time. 0:24:36.359 --> 0:24:39.439 As rabbits evolve resistance. 0:24:39.800 --> 0:24:42.520 Oh, it's really interesting. 0:24:42.680 --> 0:24:46.399 I love it. I love it so much. I can't like, 0:24:46.440 --> 0:24:47.880 I get so excited. 0:24:50.160 --> 0:24:52.200 I think this. I swear this is my last one. 0:24:52.240 --> 0:24:54.640 But I was just thinking about it. So, in these 0:24:54.760 --> 0:24:59.439 rabbits that are resistant in some way to Maxima virus, 0:24:59.480 --> 0:25:04.439 whether it's like the American rabbits that you just have 0:25:04.520 --> 0:25:08.560 the skin lesions, et cetera, how long does the virus 0:25:08.600 --> 0:25:10.399 persist in those hosts. 0:25:10.720 --> 0:25:12.800