#35 – Rustrela Virus: the Mystery of the Staggering Cats

Show notes

Since the 1970s, cats in Sweden, and later in and around Vienna, have been falling ill with a mysterious brain inflammation known as staggering disease. Affected cats develop fever, behavioral changes, a staggering gait and often paralysis of the hind legs, and most have to be euthanized. For decades Borna disease virus was the main suspect, but metagenomics finally solved the case: in 2023, rustrela virus, a close relative of rubella virus, was detected in 27 out of 29 affected cats from Sweden, Germany and Austria. Florian Krammer explains how cats catch the virus from the mice they hunt, why different mouse species carry it in Germany and Sweden, and why it has now also turned up in a mountain lion in Colorado. There is no vaccine and no treatment, and no human cases have been reported. He also introduces ViroKitty, a citizen science project in Vienna where cat owners can hand over their outdoor cats' prey for virus research.

Video of mountain lion in Colorado with staggering disease/rustrelavirus infection: https://www.youtube.com/watch?v=KtofjO4Tfds Information about rustrelavirus and staggering disease: https://www.abcdcatsvets.org/guideline-for-staggering-disease/ Project ViroKitty: https://soap.lbg.ac.at/virokitty-how-your-cat-can-become-a-virologist/

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Krammer laboratory information

Krammer Laboratory at the Icahn School of Medicine at Mount Sinai https://labs.icahn.mssm.edu/krammerlab/

Ludwig Boltzmann Institute for Science Outreach and Pandemic Preparedness https://soap.lbg.ac.at/

Ignaz Semmelweis Institute https://semmelweisinstitute.ac.at/

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Conflict of interest statement

The Icahn School of Medicine at Mount Sinai has filed patent applications relating to influenza virus vaccines and therapeutics, SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines which name me as inventor. Mount Sinai has spun out a company, CastleVax, to commercialize NDV-based SARS-CoV-2 vaccines and I am named as co-founder and scientific advisory board member of that company.

I have previously consulted for Curevac, Merck, Gritstone, Sanofi, Seqirus, GSK and Pfizer and I am currently consulting for 3rd Rock Ventures (US) and Avimex (Mexico).

My laboratory has been collaborating in the past with Pfizer on animal models of SARS-CoV-2 and with GlaxoSmithKline and VIR on the development of influenza virus vaccines and therapeutics and we are currently collaborating with Dynavax, Inspirevax and Inimmune on development of influenza virus vaccines.

My work in the on immunity and infectious diseases in the US is supported by the National Institutes of Health, but also by FluLab and Tito’s Handmade Vodka. In the past I have also received funding from the Bill and Melinda Gates Foundation, PATH and the US Department of Defense.

My work in Austria is supported by the Ludwig Boltzmann Gesellschaft and by the Ignaz Semmelweis Institute through the Medical University of Vienna.

Show transcript

00:00:05: There's no human infections described, but maybe the immunity that we have against rubella virus actually protects us.

00:00:13: These viruses are closely related.

00:00:15: people are vaccinated against Rubella Virus and so there might be a barrier through vaccination.

00:00:46: Hello everybody!

00:00:47: And welcome to this episode of Virological.

00:00:50: This was recorded on October sixth of twenty-twenty six in Vienna.

00:00:57: So today we're going to talk about disease that affects cats and for a long time was in mystery.

00:01:05: The disease is called Staggering Disease, And it's now associated with Rostrella virus.

00:01:14: But they took quite some time to figure this out and will talk the story of that.

00:01:20: Maybe little bit about rostrela virus at first.

00:01:24: Rostrelavirus is relatively closely related to rubella virus.

00:01:29: So, rubellavirus is a virus that affects humans can cause birth defects if it infects pregnant women and we have really good vaccine against it as part of the MMR vaccine.

00:01:41: so they are in.

00:01:42: MMR stands for rubeller but this virus here rostrella virus is closely related.

00:01:48: The name made up two words R-U comes from rubello because similar And then the strela comes from the straalisont region of the Baltic Sea in Germany.

00:02:01: So it's just a made-up name.

00:02:05: This virus is a positive sense single stranded RNA virus.

00:02:10: It has a genome with approximately ten thousand base pairs and The genome codes for nonstructural proteins.

00:02:19: two of them.

00:02:20: one is called B hundred fifty,the other one is the polymerase RNA-dependent polymerase, and then also a capsid and an E one and E two spike protein.

00:02:31: The virus is about seventy to eighty nanometers in diameter.

00:02:35: this that's the assumption.

00:02:38: we have a genome inside the genome is surrounded by a capside Then you have a lipid envelope And then we have the E One and E Two protein sitting there In the lipid envelopes basically forming the spike proteins.

00:02:53: It's worth mentioning that when this virus was discovered, a similar virus also was discovered.

00:02:57: That is called Ruhugovirus which has been found in bats in Uganda but rostrelia is different.

00:03:03: it not from Uganda and Europe as you will see.

00:03:07: Now little bit about the history of this virus.

00:03:10: why its relevant to disease that is causing.

00:03:14: This all started with observation In the nineteen seventies in Sweden that cats would get sick and they would get a disease that was then termed Staggering Disease.

00:03:26: So these first observations were made in Sweden, around this Milarene lake which I think is west of Stockholm And basically cats with disease symptoms where found there... ...and the same disease also was found in the nineteen nineties In Austria, Vienna and around Vienna.

00:03:46: This observation it wasn't made by Norbert Novotny.

00:03:50: They have an Eisenberg and they describe basically the same disease in cats.

00:03:56: And there was also a similar description, in the nineteen seventies-and-nineteen eighties In Lyons with basically an encephalitis in a zoo in Germany, in what reinvest fall here?

00:04:10: So this disease in cat as I mentioned is called staggering disease.

00:04:15: it starts with fever, behavioral changes and gait abnormalities so basically staggering.

00:04:23: It's really hard for them to move around in a coordinated way.

00:04:27: depression at the later stage often paralysis of their hind legs sometimes also inability to retract the claws And this is pretty severe disease often leads to death.

00:04:42: usually these cats have to be euthanized.

00:04:45: They can survive and if they survive usually it's just a partial recovery but its the severe disease.

00:04:51: It is rare, not that common But yeah...it has been observed in basically Sweden or Austria And Germany at least up to this point.

00:05:06: Cats are more affected in winter and spring, less so in summer or fall.

00:05:12: It's usually adult cats that have access to the great outdoors.

00:05:21: Back then, of course, autopsies were done... ...and histopathology for the brain was performed.

00:05:27: And it looked like a virus in cephalitis but we wasn't clear what would cause this.

00:05:34: There is this hypothesis out there in the nineties and the two-thousands, that this staggering disease was caused by Borna disease virus one.

00:05:45: We've talked about Borna Disease Virus One before.

00:05:49: it's a pretty nasty virus that causes issues in humans and horses but yeah... The idea is that the cats are getting these too.

00:05:58: But This Was Wrong!

00:06:01: That data wasn't solid enough.

00:06:03: I think New light was shed on this disease starting in the twenty twenties.

00:06:11: So, In two thousand and twenty an investigation came out that actually reported to new rubella viruses or rubellel like viruses.

00:06:21: one of them is Ruhugo virus from Uganda And second one was rostrella virus.

00:06:28: It was identified using metagenomics.

00:06:32: So typically if you look for a virus and know what your looking for, run BCR.

00:06:37: Polymerase chain reaction on genomic material that you extract from samples.

00:06:43: then you can say the virus or at least the genome is there or not.

00:06:47: but of course it doesn't work with new viruses.

00:06:53: basically sequence everything that's in a sample or the genetic material, and then you use relatively complex bioinformatics biplane to look for new sequences.

00:07:03: That could be related to viruses... And that was done here!

00:07:07: On one side this is done on bad samples from Uganda, on other side it has been done by samples of zoo animals that had died in northern Germany of encephalitis symptoms.

00:07:24: And they looked at samples from a donkey, a capybara and the red-necked wallaby... ...and found this new virus, this rostrelavirus.

00:07:35: They also sampled mice in surrounding areas including yellow necked field mice, Apodemos flavicollis.

00:07:45: These mice didn't have any symptoms but it turned out that lot of them carried these rostrella viruses.

00:07:52: The donkey had it, the capybara had it.

00:07:54: The red-necked wallaby had and yellow necked field mice had it.

00:08:00: And later on was also found that the quadi otter and main wolf have this infection.

00:08:07: So they found these new virus associated with encephalitis in a number of animals.

00:08:12: There seemed to be connection between them.

00:08:17: And then in twenty-twenty three, a new study came out that looked at tissue samples from cats that had died of staggering disease.

00:08:26: In Sweden and Germany and Austria.

00:08:29: That study found rostralovirus in twenty seven out of twenty nine of these cats basically making the connection between Rostralo virus and Staggering disease.

00:08:41: so The mystery was solved.

00:08:44: now Of course there were more investigations instead.

00:08:47: It turns out in Germany the virus is found.

00:09:17: the rodent reservoir might be different in two different countries.

00:09:22: More recently, staggering disease was also described as a mountain lion in Colorado.

00:09:28: so this is not just an European issue and I'll post video of that poor animal found on the link section below.

00:09:37: it's interesting to look at.

00:09:39: unfortunately the animal had to be euthanized.

00:09:43: Then sequence analysis was done and it seems that the European sequences cluster together, US sequences a little bit further away.

00:09:53: So to summarize we have affected areas in Sweden also Germany, Mecklenburg-Vorpommern Berlin Brandenburg Hanover Leipzig And then Austria around Vienna and Colorado.

00:10:07: Unfortunately, there is no vaccine available and not treatment.

00:10:10: So that's not much you can do for these cats.

00:10:13: And the question also as always Is this a threat to humans?

00:10:16: The virus seems to infect lot of different animals In these zoos.

00:10:20: it seems like they can go even to marsupials Like kangaroos.

00:10:27: But maybe There are no human infections described but Maybe the immunity we have against Rubella virus actually protects us.

00:10:37: These viruses are closely related, people are vaccinated against Rubella virus and so there might be a barrier through vaccination.

00:10:45: The last thing I wanted to mention here is we started the science outreach project Here in Vienna that also looks at Australia virus So this part of my Ludwig Boltzmann Institute for Science Outreach and Pandemic Preparedness And We Wanted To Work With Cat Owners And so we started a project that's called Virokitty.

00:11:09: I'll also leave the description in the link section.

00:11:12: and So, We reached out to Cat on us in Vienna you know, one of the free roaming cats tracks in any type of prey.

00:11:21: This could be a rodent this could be bird and then we do screening off these animals where in rodents were interested in hunter viruses and pornoviruses but also in rostrella virus.

00:11:32: so we want to look at the prevalence of this virus and sequence diversity of what's around in Vienna And We are planning on doing meta genomics on these animals.

00:11:46: quite a few samples, but if you live in Vienna please consider signing up for that.

00:11:52: Unfortunately we can only do this in Vienna.

00:11:54: We don't have enough capacity to collect samples outside.

00:11:58: But basically If your contact us somebody will come and pick-up Your rodents or your bird that your cat dragged in.

00:12:06: Maybe it's also important to say cats Do a lot of damage In terms of wildlife so its better To keep them inside.

00:12:12: It is also safer For the Cat.

00:12:14: Yeah!

00:12:14: That's it for today.

00:12:16: Interesting disease, relatively rare but it has been an unsolved mystery for quite some time.

00:12:22: But now is Metagenomics with new technologies that could be solved!

00:12:26: So as always if you have any questions comments concerns please write email to Virological at podcastworkstation.com and If You like the Podcasts you can support us unsteady.

00:12:38: Thanks For Listening In And Until Next Time Bye.

00:12:44: If you're enjoying the podcast and would like to support our work, visit us on Steady.

00:12:49: You'll find a link in the show notes!

00:12:52: And don't forget to follow & leave a review of your favorite podcast app.

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