As an Associate Editor for Emerging Infectious Diseases and as a frequent peer reviewer other journals, I see lots of paper that report finding a ‘new’ virus. These can be a challenge to interpret because advances in technology let us find things we’ve never been able to find before. The problem is, we can find things a lot easier and quicker than we can understand them, and it’s easy to jump to questionable conclusions.
Let’s say we look at individuals with a disease and we find a specific virus that we haven’t seen before. That’s interesting but it’s step one of many. Maybe we then test a few other animals with the same disease and find the same virus.
- Not necessarily, since we live in a microbial world, and lots of those microbes live on or in us. We have a ‘commensal microbiota’ of bacteria, viruses, fungi and parasites that we co-exist with. Some of them help us. Some can hurt us at times. For most, we live blissfully unaware of their presence.
So, finding X virus in people with Y disease could mean that it’s a cause. Or, it could mean it’s a normal inhabitant that we have finally just noticed. Or, it could be something that’s relevant but only when some other microbe starts things off.
I see lots of papers that stop at this step. They find a virus (often just genetic bits of it, not the whole virus or not evidence of live virus) and link it with a disease. Sometimes they’re right (or lucky). Sometimes, they’re not and that sends people down unnecessary paths.
The next step in the process is looking at similar but healthy individuals to see if the implicated microbe is only present in the sick ones. That’s not a guarantee it’s the cause, but it’s the next step and provides much more solid evidence.
On to the actual topic….
“Staggering disease” is a unique and interesting neurological disease that’s found in cats in some parts of Europe. Clinically, it usually causes hind limb ataxia that results in a staggering gait. Various other neurological signs can be present but hindlimb ataxia is the most consistent, obviously giving rise to the disease’s name. First described in the 1970s, the cause has been elusive but a virus has been suspected. Borna disease virus 1 (BoDV-1) was previously a leading candidate but has fallen out of favour lately.
A recent preprint (Matiasek et al) may have answered the question of what causes this disease. They started off looking for Borna disease virus in 29 cats with staggering disease from Sweden, Austria and Germany. They went 0/29, using both PCR and immunohistochemistry. That might put to rest suspicions that it is involved in the disease.
Then, they used a metagenomic approach to identify genetic material from any virus that might be present. Unlike PCR, where you must have a target, metagenomics lets you find snippets of virus genetic material that you try to stitch together into larger fragments and compare them with known viral genomes, to identify what’s there.
Using this approach, they found sequences that matched Rustrela virus (RusV) in 14/15 samples that they tested. They then developed a new PCR test for RusV and got positive results from 15/15 cats from Sweden, 8/9 from Austria and 3/5 from Germany. They followed that up with some other tests of brain tissue (in situ hybridization, immunohistochemistry) to confirm the presence of the virus. Overall, 28/29 cats tested positive with at least one of the tests. Importantly, samples from 21 cats without encephalitis or 8 cats with encephalitis of other causes were all negative.
Rustrela virus is a close relative of rubella virus (which causes rubella in people). That doesn’t mean there’s any link with people or rubella virus, but it lets us understand more about the virus. It has also previously been found in the brains of a few different mammals with neurological disease in a zoo in northern Germany.
If it’s the cause, lots of questions remain. A big one is about its reservoir. Does it circulate in cats or spillover from other species (e.g. wildlife)? That will take a lot more work to sort out, but they started looking into this by testing brains of 116 rodents from Sweden that had been caught between 1995-2019 for other studies. Using PCR, they got positive results from 8/106 (7.5%) wood mice. None of the infected mice had changes in their brain, something that would fit with a reservoir species that can carry (and spread) the virus, potentially for a long time if it doesn’t cause disease. If the virus lives in the brain, presumably cats are exposed through hunting, but a lot more work needs to be done to look at virus shedding and transmission routes.
I assume we’ll be hearing a lot more about this virus in coming years as more work gets done. It’s not a slam-dunk but this seems pretty convincing and definitely enough to launch more studies since lots of important questions remain.