Spyros Lytras Profile picture
Sep 17, 2021 12 tweets 4 min read Read on X
So, this excellent preprint came out a few hours ago and I have to say we’re getting closer to understanding where SARS-CoV-2 came from and where similar pandemic CoVs might be! researchsquare.com/article/rs-871… 🧵⬇⬇
Got home and gave it a proper read (i.e. stared at the supplementary phylogenies) and here are some interesting bits below: (I’m gonna go through the trees for some non-recombinant fragments, so fig2 here is helpful)
The fragment 3 tree is important, cause for this region BANAL103 and 52 seem veery close to SARS-CoV-2. This genome bit is probably the evolutionarily closest relative to SARS-CoV-2 to date. (need to run some dating once the seqs are out).
Also, the bat species are the usual culprits: R. pusillus (RpYN06) – w/ a wide host range & R. malayanus (RmYN02) w/ a range connecting the Indochinese peninsula to China through Yunnan.
“Interestingly, one should note that very similar SARS-CoV-2-like viruses are shared by different bat species, suggesting a possible circulation of viruses between different species living sympatrically in the same caves” – v well put by the authors!
Moving on, fragment 4 tree shows all 5 new viruses clustering closely with the RmYN02/PrC31/RpYN06 cluster sampled in Yunnan, i.e. all these viruses recently shared a common host population (bats) that moved (flew?) from one place to the other.
The pattern becomes even more intricate in fragments 10&11 where only 2 viruses share the non-SC2-like recombinant bit that RmYN02 also has.
This means that either recombination happened right after divergence of the viruses or (more likely) the recombinant bit in the other viruses got ‘overprinted’ by more recombination! Either way this suggests A LOT of opportunity for recombination btn CoVs in bats!
We talk about recombination patterns and overprinting in our preprint here if you wanna read more: biorxiv.org/content/10.110…
Oh and last thing the fragment 10 tree shows the BANAL103 and 236 clustering with the Guangdong pangolin CoV, supporting the hypothesis that pangolins get the CoVs from independent jumps from bats.
My key takeaways:
1️⃣ these viruses can quickly move through wide geographic ranges on their bat reservoir hosts
2️⃣ there's more recombination opportunities than we think
3️⃣ apart from more virus sampling we need a thorough map of horseshoe bat movement routes!
great work to all the authors involved, this is a very well presented manuscript!

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More from @SpyrosLytras

Apr 6, 2024
Some thoughts on the H5N1 situation 🦆🐄🦠 First, the situation is very concerning. this virus does not trasmit h2h, but the more animals in close contact with humans it infects the more the chance of h2h becoming a possibility. Now onto the interesting mutations:
We have shown that viruses with NP:Y52H can evade BTN3A3, a human antiviral gene against avian flu (). This mutation happens quite frequently in avian viruses.nature.com/articles/s4158…
However, H5N1s specifically are able to infect humans (at least without h2h) irrespective of their BTN3A3 evasion status. in this case it happened in birds before spilling to cattle or humans, but only in this lineage, not the one causing the recent 🦆to🐐 cases. Image
Read 6 tweets
Nov 29, 2023
🚨New paper alert! and it's one I'm really excited for! Resurrection of OAS1 from the ancestor of modern horseshoe bats blocks SARS-CoV-2 replication now out in @PLOSBiology

Here's a 🧵on how we reconstructed an ancient 🦇anti-CoV protein

doi.org/10.1371/journa…
Animals have many diverse mechanisms to restrict viral infection, some maintained for millions of years and others lost at certain points in time. In this paper we use computational and experimental approaches to go back in time in the evolution of the horseshoe bat OAS1 gene. Image
A couple of years ago, our study led by @virologist_atu @WilsonLabCITIID showed that the prenylated form of the human OAS1 protein restricts SARS-CoV-2 replication by detecting viral dsRNA in the cell.

science.org/doi/10.1126/sc…
Read 13 tweets
Jul 6, 2023
I promised some thoughts on avian H5s based on our recent results and I've decided to link these up to the current H5N1 cat outbreak in Poland. Long story short, oneoff cat to human infections should be a worry, but onward h2h transmission is unlikely with the current situation.
In our recent paper we found a human-specific inhibitor of avian IAV infection (BTN3A3) which can be evaded by a single aa substitution in either of 2 sites on the viral NP
All human-circulating IAV strains and virtually all bird to human spills of low-path viruses have these evasion substitutions. The only exception is high-path H5 viruses!
Read 15 tweets
Jun 29, 2023
It's finally out! an exciting paper almost 4 years in the making: BTN3A3 evasion promotes the zoonotic potential of influenza A viruses in @Nature Here's a 🧵 about how 🐓 influenza A viruses cross the species barrier
nature.com/articles/s4158…
the work, spearheaded by our flu aficionado @RuteMPinto started off with screening a number of ISGs (interferon-stimulated genes) with an array of pathogenic viruses, to see if expression of any of these genes stops virus replication
Soon enough, one curious result showed up! Expression of human BTN3A3, a member of a diverse protein family called butyrophilins, restricted avian IAV, but had no effect on the human IAV strains! (or any other virus we tested)
Read 21 tweets
May 25, 2023
Wee🧵about our recent paper on the origins and virological characteristics of the SARS-CoV-2 XBB variant published last week in @NatureComms with G2P-Japan, @jampei2 @SystemsVirology 🦠🧬
nature.com/articles/s4146…
Our previous paper on the BQ.1.1 variant let us understand the importance of convergence in the evolution of SC2. The emergence of XBB let us delve into a second crucial evolutionary process of SC2, recombination!
early in the pandemic we showed how recombination of Spike bits is an essential process in the closest bat virus relatives of SC2 and proposed that this will also become important in SC2's evolution once enough co-circulating diversity builds up
doi.org/10.1093/gbe/ev… Image
Read 11 tweets
Oct 28, 2022
Recently I've been too busy to engage with the latest cuckoo discussions on SARS-CoV-2 origins, but I wanted to comment on the Senator Burr report that's making the rounds, especially since they use a figure I made (!) for their fig2 help.senate.gov/imo/media/doc/…
First things first, I was never consulted about this report or had any knowledge of it before the last 24 hours.
To my understanding this is a US senate commissioned report assessing the origins of SC2. Not sure who actually wrote it (don't really care), but they've done a very VERY bad job at reporting the science on this topic... here's some thoughts:
Read 20 tweets

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