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Laboratory of Functional Viromics (LETKO)

@fviromics.bsky.social
1.3K followers 305 following 75 posts

Dr. Michael Letko’s Laboratory of Functional Viromics | we study zoonotic potential of novel viruses. For more information, check out our website: labs.wsu.edu/lofv

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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 29/09/2026
This is a great write-up from the editorial team at Nature Microbiology about our hedgehog coronavirus receptor paper and the study from Huan Yan’s group at Wuhan University, who reached the same finding independently.
nature.com
Convergent receptor use at the coronavirus One Health interface - Nature Microbiology
Two independent studies identified host species-specific aminopeptidase N as the entry receptor for hedgehog merbecoviruses, revealing convergent receptor use with alphacoronaviruses, but through a di...
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Bat1K Genome Project @bat1kgenomes.bsky.social · 23/09/2026
Where did bats come from?🦇🌍 After decades of debate, the biggest bat genome + fossil study ever done has an answer - and it’s not where anyone expected! 🤩OUR PHASE 1 FLAGSHIP is out today in nature! doi.org/10.1038/s415... A thread 🧵
doi.org
Reference genomes and fossils revise bat family phylogeny and biogeography - Nature
An updated phylogeny of bats is presented, based on new genome assemblies and many ancient fossils and including all known bat families.
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 16/09/2026
Our hedgehog coronavirus receptor study is now out in Nature Microbiology! Exciting new data has been added since the pre-print, including structure-guided mutagenesis showing species barriers, TMPRSS2 experiments and more details on the curious temperature adaptation in hedgehogs. (1/4)
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 31/07/2026
Our star post-doc, Victoria, gave a fantastic talk at ASV this year! BTW, the paper should *finally* be out soon.
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 28/06/2026
See you all in 2029!
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 28/06/2026
See you all in 2029!
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Steph N. Seifert, PhD @stephseifertphd.bsky.social · 15/06/2026
Host overlap was the strongest ecological correlate of reassortment, suggesting that opportunities for divergent viral lineages to meet matter more than prevalence alone. Of course, it's not all ecology! Molecular compatibility between genome segments acted as a second filter. (2/3)
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 04/06/2026
This is an impressive study!
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 22/04/2026
New alphaCoV receptor out today in nature! Very cool! www.nature.com/articles/s41...
nature.com
Heart-nosed bat alphacoronaviruses use human CEACAM6 to enter cells - Nature
Human CEACAM6, which is widely expressed in the lung, is identified as a receptor used by the spike proteins of Cardioderma cor (heart-nosed bat) alphacoronaviruses to enter cells.
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 06/04/2026
Our mini-review for Journal of Virology’s “new voices in virology” collection is out now. We highlight our lab’s mission, approaches, successes and visions for the future. doi.org/10.1128/jvi....
doi.org
Exploring coronavirus cell entry with functional viromics | Journal of Virology
In November of 2002, patients presenting atypical pneumonia were admitted to hospitals in Guangdong Province in the People's Republic of China (1). By April of 2003, a novel causative agent was isolat...
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 12/02/2026
A big thank you to Dr. Nick Catanzaro for visiting the LoFV this week and sharing his cool science!
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Spyros Lytras @spyroslytras.bsky.social · 28/10/2025
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!! 🥳🥳
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Spyros Lytras @spyroslytras.bsky.social · 28/10/2025
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.
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Spyros Lytras @spyroslytras.bsky.social · 28/10/2025
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.
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Spyros Lytras @spyroslytras.bsky.social · 28/10/2025
AlphaFold3 co-structure predictions were also consistent with entry when this single mutation was introduced, revealing the likely molecular interaction that enables hACE2 compatibility.
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Spyros Lytras @spyroslytras.bsky.social · 28/10/2025
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!
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Spyros Lytras @spyroslytras.bsky.social · 28/10/2025
Then we asked, since ACE2 ortholog usage seems to shift quite easily in these viruses, could nvHKU5r-CoV potentially use human ACE2?
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Spyros Lytras @spyroslytras.bsky.social · 28/10/2025
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.
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Spyros Lytras @spyroslytras.bsky.social · 28/10/2025
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.
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Spyros Lytras @spyroslytras.bsky.social · 28/10/2025
...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.
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Spyros Lytras @spyroslytras.bsky.social · 28/10/2025
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...
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Spyros Lytras @spyroslytras.bsky.social · 28/10/2025
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.
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Spyros Lytras @spyroslytras.bsky.social · 28/10/2025
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!
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Spyros Lytras @spyroslytras.bsky.social · 28/10/2025
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.
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Spyros Lytras @spyroslytras.bsky.social · 28/10/2025
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...
biorxiv.org
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...
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 27/10/2025
New pre-print! Where did the HKU5 viruses recently reported in mink come from and where might they go next? In this collaboration with the Sato lab, we explore the recombinant origins of mink HKU5 viruses and test what it would take for human ACE2 use. Intermediate hosts are important for zoonosis!
shorturl.at
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...
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Lars-Anders Carlson @lacarlson.bsky.social · 16/09/2025
I love the kind of papers that I sometimes get from the cryo-EM bot. Hedgehog coronavirus!🦔
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Steph N. Seifert, PhD @stephseifertphd.bsky.social · 17/09/2025
Excited to share our study reporting the first Sin Nombre virus (SNV) genome sequences from the Northwestern U.S., and the first ever from a vole host. www.biorxiv.org/content/10.1...
biorxiv.org
First Sin Nombre virus (Orthohantavirus sinnombreense) genome sequences from the Northwestern United States
We report the first Sin Nombre virus (SNV) genome sequences from the Northwestern United States and the first SNV sequences recovered from voles. Analysis of samples collected from 189 individual rode...
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 14/09/2025
If you haven’t already, you should check out our latest study identifying the host receptor used by merbecoviruses that circulate European and Asian hedgehogs. It’s a surprising finding that unlocks the entire group of viruses for researchers to study further!
biorxiv.org
Aminopeptidase N is a receptor for hedgehog merbecoviruses
Merbecoviruses, closely related to the highly pathogenetic Middle East Respiratory Syndrome Coronavirus (MERS-CoV), circulate in hedgehogs throughout Europe and Asia, raising concerns about zoonotic t...
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 04/09/2025
This was a large team effort. Big thank you to our structural collaborator, James Rini at University of Toronto, Craig Wilen at Yale, the Baric lab at UNC, our Italian collaborators for discovering these viruses and sharing cool sequence data, and of course, Vic, the talented postdoc in my lab.(6/6)
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 06/09/2025
🧐 if you know, then you know www.biorxiv.org/content/10.1...
media.tenor.com
a cat is petting a hedgehog in a black and white photo with the words `` happy hedgegie hugs '' .
ALT: a cat is petting a hedgehog in a black and white photo with the words `` happy hedgegie hugs '' .
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 06/09/2025
🧐 if you know, then you know www.biorxiv.org/content/10.1...
media.tenor.com
a cat is petting a hedgehog in a black and white photo with the words `` happy hedgegie hugs '' .
ALT: a cat is petting a hedgehog in a black and white photo with the words `` happy hedgegie hugs '' .
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 04/09/2025
To expand on the RBD clade classifications from our last paper: CLADE 1 = MERS-CoV, HKU4 = DPP4 users CLADE 2 = HKU5 complex, HKU25, H.Savii = ACE2 users CLADE 3 = PDF2180, NeoCoV = ACE2 users CLADE 4 = ErinCoVs (all of them) = APN users Such receptor diversity for one subgenus! 🤩 (5/6)
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 04/09/2025
We also provide not one, but TWO cryo-EM co-structures of ErinCoV RBDs bound to hedgehog APN. Both German and Italian hedgehog coronaviruses interact with hedgehog APN identically. Binding assays show that ErinCoVs have a lower affinity for APN than other CoVs have for their receptors. (4/6)
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 04/09/2025
Aminopeptidase N- the classic alpha-CoV receptor - facilitates ErinCoV entry. And we don't show this for just one virus, we show it for all of them. Every merbecovirus in hedgehogs across Europe and Asia- from ErinCoV-12-19 to HKU31 - all use APN. This is a first for beta-CoVs! (2/6)
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 04/09/2025
New preprint! If some merbecoviruses use DPP4 and others use ACE2, what do those hedgehog merbecoviruses use?! As it turns out, neither! In our latest study, we uncover the "missing" receptor for the MERS-related viruses in hedgehogs. [These findings were first shared at ASV this year] (1/6)
tinyurl.com
Aminopeptidase N is a receptor for hedgehog merbecoviruses
Merbecoviruses, closely related to the highly pathogenetic Middle East Respiratory Syndrome Coronavirus (MERS-CoV), circulate in hedgehogs throughout Europe and Asia, raising concerns about zoonotic t...
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 04/09/2025
New preprint! If some merbecoviruses use DPP4 and others use ACE2, what do those hedgehog merbecoviruses use?! As it turns out, neither! In our latest study, we uncover the "missing" receptor for the MERS-related viruses in hedgehogs. [These findings were first shared at ASV this year] (1/6)
tinyurl.com
Aminopeptidase N is a receptor for hedgehog merbecoviruses
Merbecoviruses, closely related to the highly pathogenetic Middle East Respiratory Syndrome Coronavirus (MERS-CoV), circulate in hedgehogs throughout Europe and Asia, raising concerns about zoonotic t...
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Barbara A. Han @bahanbug.bsky.social · 27/08/2025
Breakthroughs happen when diverse expertise is woven together. Collaboration can be messy—different vocabularies, different tools—but it’s worth it. We made a video with @MinuteEarth about it. 🎥 @fviromics.bsky.social @payeldas.bsky.social & Drew Kramer #EEID
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Healthcare-Global @healthcare-global.bsky.social · 25/07/2025
www.nature.com/articles/s41...
nature.com
HKU5 bat merbecoviruses engage bat and mink ACE2 as entry receptors - Nature Communications
Alfajaro et al identify that a bat MERS-like coronavirus HKU5 uses ACE2 as a receptor from its natural bat reservoir Pipistrellus abramus and American mink. Structural analyses demonstrate a unique in...
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Simon Lab @vivianasimonlab.bsky.social · 17/07/2025
Always great to see Simon Lab Alumni go on to achieve great things! Dr. Michael Letko gave an excellent keynote at #ASV2025 on "Uncovering novel receptor use in beta-coronaviruses with functional viromics" check out his lab's work here: labs.wsu.edu/lofv/ @amersocvirology.bsky.social
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Steph N. Seifert, PhD @stephseifertphd.bsky.social · 14/07/2025
🚨 Our team just released a reproducible Docker pipeline for RNAseq assembly and annotation designed for nonmodel organisms! We're using it to explore how bats manage viral infections, but it's built for broad utility in wildlife transcriptomics. @viralemergence.org www.biorxiv.org/content/10.1...
biorxiv.org
TATAT: a containerized software for generating annotated coding transcriptomes from raw RNA-seq data
Motivation: Many transcriptome creation workflows are not standardized, are difficult to install or share, prone to breaking as dependencies update or cease to be maintained and are resource intensive...
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 10/07/2025
LoFV will be all over ASV in Montreal this year! I am giving a plenary talk Monday evening and will share an all new study that hasn’t been pre-printed. Also, look out for our talented post-doc, Victoria Jefferson, on Wednesday (P26-15) and skilled collaborator, Nick Catanzaro, on Tuesday (W13-6).
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Bjorkman Lab @ Caltech @bjorkman-lab.bsky.social · 04/07/2025
Exciting news! A few weeks ago, the TWiV podcast reviewed a paper from Michael Letko's lab (@fviromics.bsky.social) featuring one of our graduate students as a co-first author. Give it a listen! www.microbe.tv/twiv/twiv-12...
microbe.tv
TWiV 1223: Someone is guano be sick
TWiV reviews RFK Jr.''s MAGA report with non-existent literature citations, a new fungus that could further devastate North American bats, surveillance of avian influenza viruses through bird guano in...
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 12/06/2025
Our study assessing global merbecovirus entry and showing the receptor for HKU5 viruses was featured by the editors on the Nature Communications highlights page. Give it a read if you haven’t already! www.nature.com/collections/...
nature.com
Microbiology and infectious diseases
This page highlights recent articles on all aspects of bacteriology, mycology, parasitology and virology, covering the biology of pathogens, host-pathogen ...
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 04/06/2025
Here’s a great write up of our latest work with HKU5 coronaviruses from the WSU press office! news.wsu.edu/press-releas...
news.wsu.edu
Bat viruses similar to MERS have potential to jump to humans
A new WSU-led study finds that a little-known group of bat viruses may be just one mutation away from infecting humans, highlighting the risk of a potential future pandemic.
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Laboratory of Functional Viromics (LETKO) @fviromics.bsky.social · 03/06/2025
Our study screening merbecoviruses for receptor tropism and identifying the receptor for HKU5 coronaviruses was highlighted in This Week in Virology with Vincent Racaniello!What great discussion of the study! www.microbe.tv/twiv/twiv-12...
microbe.tv
TWiV 1223: Someone is guano be sick
TWiV reviews RFK Jr.''s MAGA report with non-existent literature citations, a new fungus that could further devastate North American bats, surveillance of avian influenza viruses through bird guano in...
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Spyros Lytras @spyroslytras.bsky.social · 30/05/2025
very nice work from the @fviromics.bsky.social and Baric labs uncovering some of the ways these merbecoviruses can use ACE2 as their entry receptor! www.nature.com/articles/s41...
nature.com
ACE2 from Pipistrellus abramus bats is a receptor for HKU5 coronaviruses - Nature Communications
This work shows that receptor use in merbecovirus is clade-specific by clustering them into clades based on the receptor-binding domain (RBD) of their spike proteins. While MERS-CoV and its close rela...
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Tim Sheahan @timothysheahan.bsky.social · 28/05/2025
New paper about ACE2 using Merbecovirus. Hot stuff. So hot but you can't Letko. @fviromics.bsky.social and Nick Catanzaro. www.nature.com/articles/s41... #ACE2 #emergingviruses #bats #batman #MERS #HKU5
nature.com
ACE2 from Pipistrellus abramus bats is a receptor for HKU5 coronaviruses - Nature Communications
This work shows that receptor use in merbecovirus is clade-specific by clustering them into clades based on the receptor-binding domain (RBD) of their spike proteins. While MERS-CoV and its close rela...
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