Evolutionary spillover of SARS-CoV-2?

We found a close relative, but not close enough to tell us exactly where the SARS-CoV-2 virus came from. Jesse Bloom explains how this has led to two theories for how the virus has acquired its seemingly novel genetic changes…

Jesse - Well, there are two possible theories. One possible theory is that somehow it got there by natural infection -  it naturally infected some human who travelled there or some animal that was moved there. The other possibility is, it's known that there were a number of labs in Wuhan that were collecting large numbers of these bat SARS related coronaviruses and bringing them back to Wuhan to study. So, it's also possible that scientists collected a similar virus, brought it back to Wuhan, and then there was some sort of accident.

Julia - Almost all major outbreaks of infectious diseases in humans have occurred when viruses, bacteria, or parasites jump from an animal into a human.

Chris - The black death in the middle ages, the most deadly pandemic in recorded history, was caused by a bacterium that spread from wild prairie dogs into black rats, then to their fleas and ultimately to us humans. Flu pandemics begin in birds.

Julia - And, as we heard with SARS and MERS, both viruses originated in horseshoe bats and via two different intermediate species, palm civets and camels, which were able to find themselves inside a human host.

Chris - This evolutionary spillover has been the leading theory behind the differences we observe in the SARS-CoV-2 genome.

Julia - Aris Katzourakis explains.

Aris - In the hunt for trying to work out where these viruses, the lineage are called sarbecoviruses, have come from, scientists have read the genome of isolates of SARS CoV2 and they've compared that to other viruses that are genetically related to SARS CoV2 and tried to use that to disentangle these kinds of patterns of transmission. By comparing the sequence to similar sequences in bats or pangolins or other mammals that harbour sarbecoviruses, we can produce an evolutionary tree and try and work out where within this diversity of viruses SARS CoV2 sits. It's generally nested in the lineage of viruses that includes lots of bats viruses. and so, while we're not necessarily able to have the one precise bat that led to the transmission to SARS CoV2 and to COVID, it certainly seems to be the case that this is part of a larger family of viruses that includes lots of viruses found in bats.

Julia - Researchers have been working tirelessly to find a closer relative of SARS CoV2 in the wild, as this could bring us closer to where this virus made the jump.

Aris - I think it's probably fair to say that people have been sampling as intensely as they possibly can for this virus, subject to the constraints and the realities of the fact that you can't pick out every single mammal. One thing that is sometimes the case, the real clear example of direct ancestry, is when your sampled sequences form a cone-like structure in your phylogenetics tree with your one sequence of interest sticking out from the tip of that cone. We don't exactly have that for SARS CoV2, but we certainly have a lot of bat-like viruses surrounding these sequences of interest.

Julia - While we still haven't found the intermediates or closer relatives we would expect to see if a virus had made a jump from animals to humans, that doesn't mean it isn't out there.

Aris - If you think about HIV and the search for the ancestor of HIV, it took quite a while to find the exact lineages of chimpanzees, for example, that are most closely related to circulating HIV. And finding the direct ancestor, the actual chimp behind the bush that gave that initial transmission event, that's not something that we still have. We don't have that one perfect sequence there, although it's completely obvious now that there has been transmission from chimpanzees for HIV-1. With SARS 1, we also saw a series of false dawns in the search for an ancestor of that outbreak. It took a while to settle on the most likely source species. It's just a matter of the vastness of the range. There are over a thousand species of bats, and there are so many different colonies to sample that finding that one direct ancestor might be impossible.

Julia - So, just because we haven't found it yet doesn't mean that it doesn't exist?

Aris - Yeah, absolutely.

Julia - Some of the other reasons researchers are still convinced this virus emerged from nature has come from information that revealed rare animals, which can host coronaviruses, had been present in wet markets in Wuhan, which may make it very difficult to find the intermediate scientists are after.

Chris - In addition, early tracking of the virus suggests it may have been present in multiple wet markets at once, potentially indicating a batch of animals or different traders were the sources of infection.

Julia - Work is continuing to try to find a natural reservoir of a closer relative of SARS CoV-2.