Laboratory of Functional Viromics (LETKO)

I love the kind of papers that I sometimes get from the cryo-EM bot. Hedgehog coronavirus!🦔

LRP8 is a receptor for tick-borne encephalitis virus - Nature LRP8, an apolipoprotein E and reelin receptor with high expression in the brain, is a receptor for tick-borne encephalitis virus.

www.nature.com/articles/s41...

Stunning work from the Chandran lab!

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...

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...

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...

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!

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)

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 '' .

🧐 if you know, then you know

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

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 '' .

🧐 if you know, then you know

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

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)

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)

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)

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...

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)

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)

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)

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)

We also screened APN orthologues from 30 different species to demonstrate remarkably limited species tropism for ErinCoVs. Of concern though, ErinCoVs seem readily compatible with APN from cats and rats. (3/6)

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)

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...

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)

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

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...

www.nature.com/articles/s41...

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

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...

🚨 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...

If you aren’t completely tired of us by then, check out my flash talk and poster on Thursday (W55-10). Really looking forward to sharing new work and talking science!

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).

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...

Bat-specific adaptations in interferon signaling and GBP1 contribute to enhanced antiviral capacity - Nature Communications Bats harbor diverse viruses but it’s less clear how they tolerate infection. Here, by characterizing innate immune responses in bat cells the authors show that IFN-beta signaling resists antagonistic ...

🚨Our new study out today in Nature Communications. Bats can asymptomatically host multiple viruses while remaining apparently healthy. Here we identify how interferon-mediated responses protect bats and identify molecular adaptations in GBP1. #LZCI
Link: www.nature.com/articles/s41...

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 ...

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/...

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.

Here’s a great write up of our latest work with HKU5 coronaviruses from the WSU press office! news.wsu.edu/press-releas...

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...

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...

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...

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...

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