Laboratory of Functional Viromics (LETKO)

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

In our latest study we used alphafold 3 to predict the interaction between HKU5 virus spike protein and its receptor, ACE2. Using a 2021-based dataset, AF3 produced a new interface that has now been validated by other groups with cryoEM. What other new interactions can AF3 show us? rdcu.be/en7Dy

(I encourage everyone to check out supplemental figure 6 for the comparison. Yes, you have to download the supplemental information. It’s good for you.)

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...

There’s plenty left to uncover. The merbecovirus are full of surprises. Check out the paper - we can’t wait to share more soon! (5/5)
rdcu.be/en7Dy

This was a lot of hard work from many groups. Special thank you to Nick Catanzaro, Boyd Yount and the rest of the talented folks in Ralph Baric’s lab at UNC, Ziyan Wu in Pamela Bjorkman’s lab at Caltech and Victoria Jefferson, the amazingly skilled postdoc graciously working in my lab. (4/5)

…demonstrate the remarkable power of AlphaFold 3’s abilities to identify a novel viral host interaction! Now that other groups have published co-structures of HKU5:ACE2, we can validate AlphaFold’s predictions of the interaction and further extrapolate to other HKU5 strains. (3/5)

In this study, we identified bat ACE2 as the receptor the HKU5 complex of coronaviruses, validate our pseudotype assays with a live viral clone, explore spike features related to HKU5 cross-species compatibility, present a cryo-EM derived HKU5 spike trimmer structure, and…(2/5)

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...

Our study screening the majority of all published Merbecovirus RBD’s for cell entry phenotypes is now published in Nature Communications!
(1/5)
shorturl.at/gYz4E

Bat Cells in a Dish Offer a Tool to Study Their Viral Responses Bats harbor viral human pathogens without getting sick. A new cell line could open doors to new therapies based on these flying mammals’ immune secrets.

Bat cells for virology and innate immunology.

Sneha Khedkar highlights our study in The Scientist: www.the-scientist.com/bat-cells-in...

Link to original paper: journals.plos.org/plosbiology/...

@fviromics.bsky.social @stephseifertphd.bsky.social

A graphic for the Marie Skłodowska-Curie Actions (MSCA), showing a historical portrait of Marie Skłodowska-Curie overlaid with an image of four young researchers walking down a hallway. The European Commission logo is in the top left. Text reads: "Marie Skłodowska-Curie Actions – €404.3 million to support postdoctoral researchers”

Choose Science. Choose Europe.

A new Marie Skłodowska-Curie Actions Postdoctoral Fellowships 2025 call is now open.

With a budget of €404.3 million, it will support around 1,650 researchers from Europe and beyond.

Apply by 10 September → europa.eu/!fBTMgF

Top left: Primary cells were isolated from brain, lung, kidney, liver, and spleen of a single C. perspicillata bat. Bottom left: CaPsm-K primary and immortalized cells were transfected with 10 μg of poly (I:C) chemically labeled with rhodamine (pIC-Rho) for 16 h. Following fixation, cells were stained with antibodies against GAPDH and DAPI and visualized by confocal microscopy. Scale bars represent 25 μm. Right: Clonal transduced kidney cells infected with Seoul virus (SEOV) were monitored by end-point microscopy for Seoul nucleocapsid protein.

Research on the #bat innate #ImmuneResponse to pathogens is hindered by a lack of lab reagents. @fviromics.bsky.social @stephseifertphd.bsky.social @virology.bsky.social &co generate new bat #CellLines, enabling studies on viral susceptibility & immune responses @plosbiology.org 🧪 plos.io/4jkXukf

Top left: Primary cells were isolated from brain, lung, kidney, liver, and spleen of a single C. perspicillata bat. Bottom left: CaPsm-K primary and immortalized cells were transfected with 10 μg of poly (I:C) chemically labeled with rhodamine (pIC-Rho) for 16 h. Following fixation, cells were stained with antibodies against GAPDH and DAPI and visualized by confocal microscopy. Scale bars represent 25 μm. Right: Clonal transduced kidney cells infected with Seoul virus (SEOV) were monitored by end-point microscopy for Seoul nucleocapsid protein.

Research on the #bat innate #ImmuneResponse to pathogens is hindered by a lack of lab reagents. @fviromics.bsky.social @stephseifertphd.bsky.social @virology.bsky.social &co generate new bat #CellLines, enabling studies on viral susceptibility & immune responses @plosbiology.org 🧪 plos.io/4jkXukf

On the cover of the Journal of Virology this month with all our bat colleagues! #Bats #LZCI @stephseifertphd.bsky.social

Associated article: journals.asm.org/doi/10.1128/...

🚨Latest BAT publication now out in @plosbiology.org with @fviromics.bsky.social @stephseifertphd.bsky.social and others. #PLOSBiology 🦇

Proud of our PhD candidate, Victoria Gonzalez! #LZCI

journals.plos.org/plosbiology/...

More detailed post from my colleague, Dr. Letko: bsky.app/profile/fvir...

Expanding the bat toolbox: Carollia perspicillata bat cell lines and reagents enable the characterization of viral susceptibility and innate immune responses Research on the bat innate immune response to pathogens has been hindered by a lack of laboratory reagents. This study developed approaches for generating bat cell lines and produced new bat cell line...

This project was in collaboration with @seifertstephphd.bsky.social, @virology.bsky.social, @jangralab.bsky.social, Alison Kell and Christine Portfors.
For the paper: tinyurl.com/ymfduzjw
For the cells: tinyurl.com/2w5z48ej

Important: we immortalized them and deposited some cells with BEI/ATCC. Some of the only bat cell lines added to the collection in decades. Note: The Carollia-kidney-SV40 cells are available now (Cat#NR-59778). We are still working with ATCC to release the Ckg9 cells (Cat#NR-59779)- sometime soon.

Expanding the bat toolbox: Carollia perspicillata bat cell lines and reagents enable the characterization of viral susceptibility and innate immune responses Research on the bat innate immune response to pathogens has been hindered by a lack of laboratory reagents. This study developed approaches for generating bat cell lines and produced new bat cell line...

Our study developing new bat cell lines is now published with PLoS Biology! We made new bat cell lines for virology research that are immunocompetent and support entry and replication of orthohantaviruses and several others. tinyurl.com/ymfduzjw

Are bats tolerant of all viruses? With a comparative -omics approach, we show that Egyptian fruit bat cells show both antiviral and pro-inflammatory immune responses to infection with Zika virus while our Jamaican fruit bat cells are not susceptible.
www.biorxiv.org/content/10.1...

These data are complementary to reports of pathogenesis in bats challenged with ZIKV in vivo. Big congrats to my postdoc, Dr. Alexander Brown, and @annafagre.bsky.social who co-lead this study along with @ricardoriveroh.bsky.social @speranzalab.bsky.social @fviromics.bsky.social @viralemergence.org