Spyros Lytras

Meta-virus resource (MetaVR): expanding the frontiers of viral diversity with 24 million uncultivated virus genomes Abstract. Viruses are ubiquitous in all environments and impact host metabolism, evolution, and ecology, although our knowledge of their biodiversity is st

🦠🧪🧬🚨 New paper and database alert: the new IMG/VR release is now MetaVR ! We have a new website - meta-virome.org - with quick search capabilities for the >24M viruses, >12M vOTUs, and >42M protein clusters (including >790k with predicted structures !). academic.oup.com/nar/advance-...

Avian-origin influenza A viruses tolerate elevated pyrexic temperatures in mammals Host body temperature can define a virus’s replicative profile—influenza A viruses (IAVs) adapted to 40° to 42°C in birds are less temperature sensitive in vitro compared with human isolates adapted t...

Big congrats to Matt Turnbull @samjwilsonphd.bsky.social and all co-authors!! 🎉🎉

New paper in @science.org showing how the interaction between flu PB1 and host ANP32A control how flu can replicate in higher body temperatures! 🦆🦆🦆

www.science.org/doi/10.1126/...

Amazing example of influenza cheat/cooperator cycles in this recent paper - the repeatability of the oscillatory cycles is so striking

Congrats to @alnajifg.bsky.social , @christopherbrooke.bsky.social , @vignuzzilab.bsky.social & friends

www.biorxiv.org/content/10.1...

🧪 #socialviruses

Great to be teaching about structural predictions and metagenomic discovery of diverse viruses at @virus-metagenomics.bsky.social !

And even greater to be visiting sunny Stellenbosch! ☀️☀️

😍😍🍻🍻

thanks Martin!

thanks Philippe! that'd be great!

thanks Mart! It'll great to be there! 😁

thank you Cadhla!!

thank you Milot!

The Antigen Evolution & Design lab will focus on using AI-enabled methods to uncover molecular interactions within antigen protein sequences and structures. This approach will be used for designing better, broader immunity vaccines.

More info will follow soon, stay tuned! 😁😁

Guess the news is officially out! Extremely excited to announce that I will be starting my own laboratory at Institut Pasteur @pasteur.fr this coming spring!

Slight change to my office window view from Tokyo Tower🗼 to the Tour Eiffel. 🇫🇷

Great to have you over Mahan!!! 😁😁😁 A very fun trip and the start of some exciting science collabs soon! 👀👀

Diagram showing how sand fly saliva changes fibroblast state to promote arbovirus infection.

New paper out in iScience @cellpress.bsky.social
We show that #sand_fly biting reprograms skin fibroblasts, making them more permissive to virus infection
=> #fibroblasts aren’t bystanders, they help define severity/clinical outcome to infection AND #vector biting is key
👉 doi.org/10.1016/j.is...

Big thanks to Vic Jefferson, Nick Catanzaro, Ralph Baric and Michael Letko @fviromics.bsky.social and big congrats to
@jarelelgin.bsky.social
, our talented PhD student who led the work!! 🥳🥳

The bat viruses with the closest spike or loop2 to that of nvHKU5r-CoV were also sampled in provinces with primary mink fur processing and wholesale hubs, further implicating fur farming as an important risk factor for virus spillover.

Lastly we did comprehensive recombination and molecular dating analysis to explore the origins of this nvHKU5r-CoV. Our findings support that the virus transmitted from bats to mink within the last decade, consistent with an expansion of mink fur farming in China.

AlphaFold3 co-structure predictions were also consistent with entry when this single mutation was introduced, revealing the likely molecular interaction that enables hACE2 compatibility.

Using a safe, replication competent VSV system expressing the nvHKU5r-CoV spike we did passaging in mixed cells expressing both Pabr and hACE2. To our surprise, the spikes acquired a single mutation on the loop2, R548S, which enabled hACE2 usage!

Then we asked, since ACE2 ortholog usage seems to shift quite easily in these viruses, could nvHKU5r-CoV potentially use human ACE2?

We further confirmed our pseudovirus results with luciferase reporter live virus, showing that nvHKU5r-CoV specifically replicated well in both PabrACE2 and nvACE2 expressing cells.

Impressively, AlphaFold3 predictions of RBD-ACE2 pairs were very consistent with pseudovirus results! RBDs with ACE2 entry had consistent binding footprints while RBDs without entry were predicted to bind inaccessible parts of the ACE2s.

...the only two long loop2 RBDs that can use nvACE2 being nvHKU5r-CoV and Q265, but not WZ2! This shows that loop2 is a key determinant for enabling the use of non-bat ACE2s.

Taking these RBDs in the lab, we show with pseudovirus assays that all HKU5r-CoVs can use their native P abramus ACE2, but only few can use mink ACE2, especially ones with long loop2s...

This part of the RBD corresponds to a loop in the RBD structure called loop2, known to have different lengths between HKU5r-CoVs. By examining the evolution of the loop2 we show a single deletion to a shorter genotype which has in turn recombined into many different RBDs.

However, just like all CoVs merbecoviruses are notorious for recombining parts of their genome, especially the spike. Looking more closely, we detected one small part of the RBD where nvHKU5r-CoVs were curiously closer to another bat virus, Q265!

The mink HKU5 virus (nvHKU5r-CoV) was sampled in Shendong and seems to be overall closest to different bat HKU5s sampled in P. abramus bats across south and east China. 🦇
When focusing on the spike and RBD, one virus, WZ2, sampled in Zhejiang, is the single closest relative.

Structural and phenotypic plasticity of the RBD loop2 region is a key determinant for HKU5r-CoVs’ emergence in mink The emergence of novel coronaviruses from animal reservoirs continues to pose a significant zoonotic threat. Here, we investigate the evolutionary origins and virological properties of a recently repo...

New preprint alert!! 🚨🚨🚨in collaboration with the Letko @fviromics.bsky.social and Baric labs!

Just in case you're tired of sarbecoviruses, this time we looked at ACE2-using merbecoviruses! specifically the first HKU5r-CoVs detected in mink a couple of years ago.

www.biorxiv.org/content/10.1...

🎉 Fletcher lab PhD student Emma Davies reflecting on her prize winning talk - we’re super proud of you Emma - many congrats! 🎉

@cvrinfo.bsky.social @uofgsii.bsky.social @uofgmvls.bsky.social

Huge congratulations to Emma Davis, the winner of 2025's Early Career Microbiologist of the Year prize! We agree with Emma that all of the finalists' talks were brilliant and a massive well done to everyone involved!