4 ms·

Not necessarily a new path, but a previously unknown path. Any place that bats directly interact with ‘land mammals’ leads to a mess of viral recombination and

Not necessarily a new path, but a previously unknown path. Any place that bats directly interact with ‘land mammals’ leads to a mess of viral recombination and reassortment… hence why the agriculture/wild interface in China is the site of so many spillovers. Rats especially carry similar viruses with many features that increase tropism, so the fact that rats are feeding on bats means we’re going to get a ton of crossover viruses especially well suited for transmission in mammals. One such study’s key paragraph… > While uncommon for coronaviruses of bats, furin cleavage sites are commonly found in coronaviruses of rodents and it is perhaps fitting to note that proteolytic processing of the coronavirus spike protein was first recognized in the model rodent coronavirus, murine hepatitis virus, MHV-A59 [53], with later analyses demonstrating the importance of furin for the proteolytic cleavage and function of its spike protein [54]. https://www.sciencedirect.com/science/article/pii/S2352771421000720 https://www.sciencedirect.com/science/article/pii/S235277142...

neom 1y ago
I don't think that is possible in practice? Rats and Bats diverged some 60 million years ago, they're far too host specific for anything new, and they have the same coevolution as bats to paramyxo and coronaviruses, I would presume that makes them immunologically resistant and ecologically poor hosts for any strains. Edit, in fact the paper you link says exactly what I said I think? Rodent coronaviruses already evolved to use furin long ago. I think this paper just makes it even less likely tbh.
- firstplacelast 1y ago
  Might be wrong about this, but being so far removed and seemingly immunologically resistant is exactly what makes it a dangerous combination. Viruses mutate and recombine at an astonishing rate, so 99.9999% (?) of viral entities won't be able to make the jump between these species, but the one that can might have devastating consequences as it will be wildly different from anything that has infected rats before (and from there it's more likely to infect other mammal populations). The more exposure between these populations the higher the likelihood that a crossover event occurs.
  - neom 1y ago
    high mutation rate != high crossover rate, and immunological resistance != susceptibility to novel evolution. (it's actually the other way around) Also to be super clear, I'm not saying rats are immune to bat viruses, I'm just saying in reality it's is too divergent for functional crossspecies transmission and both rats and bats already have their own established, evolved coronavirus ecosystems that solve the same problems (like furin cleavage above). It seems to me near impossible it could actually happen.
    - mikeyouse 1y ago
      It’s incredibly common for bats and rats to be coinfected with the same viruses… this is literally why we were looking at pangolins and raccoon dogs and mink for SC2 and at masked palm civets and ferrets for SC1. The term of art here is “intermediate host”. The virus doesn’t need to make the animal sick to increase its human transmission risk, it just needs to infect its cells and be in the same host as other circulating viruses to get the crossover and recombination events. From early host analysis, > For a precursor virus to acquire the genomic features suitable for human ACE2 receptor binding, an animal host would likely have to have a high population density to allow natural selection to proceed efficiently (27). It is interesting to note that rodent betacoronaviruses have the polybasic cleavage site (38). Considering the above, surveillance and whole genomic analysis of CoVs from rodents are important to elucidate whether these species have any role in the transmission cycle of the virus and to detect the emergence of possible recombinants involving CoVs from these species and those from bats. However, there is not yet any evidence on the role of rodents or squirrels as intermediate hosts. https://pmc.ncbi.nlm.nih.gov/articles/PMC7297130/ https://pmc.ncbi.nlm.nih.gov/articles/PMC7297130/ Or more direct examination of the FCS issue between rats and bats: > Here, we examine the spike protein across coronaviruses identified in both bat and rodent species and address the role of furin as an activating protease. Utilizing two publicly available furin prediction algorithms (ProP and PiTou) and based on spike sequences reported in GenBank, we show that the S1/S2 furin cleavage site is typically not present in bat virus spike proteins but is common in rodent-associated sequences, and suggest this may have implications for zoonotic transfer. We provide a phylogenetic history of the Embecoviruses (betacoronavirus lineage 2a), including context for the use of furin as an activating protease for the viral spike protein. From a One Health perspective, continued rodent surveillance should be an important consideration in uncovering novel circulating coronaviruses. https://www.sciencedirect.com/science/article/pii/S2352771421000720 https://www.sciencedirect.com/science/article/pii/S235277142...

neom 1y ago

I don't think that is possible in practice? Rats and Bats diverged some 60 million years ago, they're far too host specific for anything new, and they have the same coevolution as bats to paramyxo and coronaviruses, I would presume that makes them immunologically resistant and ecologically poor hosts for any strains. Edit, in fact the paper you link says exactly what I said I think? Rodent coronaviruses already evolved to use furin long ago. I think this paper just makes it even less likely tbh.

firstplacelast 1y ago
Might be wrong about this, but being so far removed and seemingly immunologically resistant is exactly what makes it a dangerous combination. Viruses mutate and recombine at an astonishing rate, so 99.9999% (?) of viral entities won't be able to make the jump between these species, but the one that can might have devastating consequences as it will be wildly different from anything that has infected rats before (and from there it's more likely to infect other mammal populations). The more exposure between these populations the higher the likelihood that a crossover event occurs.
- neom 1y ago
  high mutation rate != high crossover rate, and immunological resistance != susceptibility to novel evolution. (it's actually the other way around) Also to be super clear, I'm not saying rats are immune to bat viruses, I'm just saying in reality it's is too divergent for functional crossspecies transmission and both rats and bats already have their own established, evolved coronavirus ecosystems that solve the same problems (like furin cleavage above). It seems to me near impossible it could actually happen.
  - mikeyouse 1y ago
    It’s incredibly common for bats and rats to be coinfected with the same viruses… this is literally why we were looking at pangolins and raccoon dogs and mink for SC2 and at masked palm civets and ferrets for SC1. The term of art here is “intermediate host”. The virus doesn’t need to make the animal sick to increase its human transmission risk, it just needs to infect its cells and be in the same host as other circulating viruses to get the crossover and recombination events. From early host analysis, > For a precursor virus to acquire the genomic features suitable for human ACE2 receptor binding, an animal host would likely have to have a high population density to allow natural selection to proceed efficiently (27). It is interesting to note that rodent betacoronaviruses have the polybasic cleavage site (38). Considering the above, surveillance and whole genomic analysis of CoVs from rodents are important to elucidate whether these species have any role in the transmission cycle of the virus and to detect the emergence of possible recombinants involving CoVs from these species and those from bats. However, there is not yet any evidence on the role of rodents or squirrels as intermediate hosts. https://pmc.ncbi.nlm.nih.gov/articles/PMC7297130/ https://pmc.ncbi.nlm.nih.gov/articles/PMC7297130/ Or more direct examination of the FCS issue between rats and bats: > Here, we examine the spike protein across coronaviruses identified in both bat and rodent species and address the role of furin as an activating protease. Utilizing two publicly available furin prediction algorithms (ProP and PiTou) and based on spike sequences reported in GenBank, we show that the S1/S2 furin cleavage site is typically not present in bat virus spike proteins but is common in rodent-associated sequences, and suggest this may have implications for zoonotic transfer. We provide a phylogenetic history of the Embecoviruses (betacoronavirus lineage 2a), including context for the use of furin as an activating protease for the viral spike protein. From a One Health perspective, continued rodent surveillance should be an important consideration in uncovering novel circulating coronaviruses. https://www.sciencedirect.com/science/article/pii/S2352771421000720 https://www.sciencedirect.com/science/article/pii/S235277142...