Jérémy Dufloo
@jeremydufloo.bsky.social
300 followers 350 following 35 posts
Postdoc in Rafael Sanjuán's lab (Universidad de Valencia) studying viral emergence experimentally | Former PhD in Olivier Schwartz's lab (Institut Pasteur) studying antibody responses against HIV-1 and SARS-CoV-2
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jeremydufloo.bsky.social
Congratulations François !! 👏
jeremydufloo.bsky.social
Thanks Maria! 😊🙏🏻
jeremydufloo.bsky.social
Thrilled to have been awarded a Ramon y Cajal 5-year tenure-track contract to continue working on viral entry (and more!) with @rafa-sanjuan.bsky.social at @i2sysbio.es and @uv.es 😀🎉
jeremydufloo.bsky.social
Thanks a lot Spyros! Glad you liked them! 🙏🏻☺️
jeremydufloo.bsky.social
I'd like to warmly thank all the collaborators involved, especially in the Sanjuán and Rey labs, in particular Ignacio Fernández (not on Bluesky), co-first author of the study! Hope you'll enjoy the read! 📚
jeremydufloo.bsky.social
Altogether, this highlights the diversity in protein and glycan receptor usage among embecoviruses, and suggests that the embecovirus RBD is a highly versatile structure that can accommodate highly divergent sequences to achieve novel receptor specificities.
jeremydufloo.bsky.social
Finally, Ignacio used cryoEM to obtain the structure of the PHEV spike ectodomain. This revealed that in contrast to all other embecovirus spikes structurally resolved (OC43, HKU1, MHV), the PHEV spike spontaneously adopts open conformations, allowing interaction with DPEP1.
jeremydufloo.bsky.social
This allowed us to identify critical residues at the interface. Morevover, this revealed that despite variations in RBD sequences and receptor usage , the structural elements involved in receptor recognition are conserved across embecoviruses.
jeremydufloo.bsky.social
Ignacio Fernández, from Félix Rey's lab, beautifully obtained the X-ray structure of DPEP1 in complex with the PHEV RBD.
jeremydufloo.bsky.social
DPEP1 was a PHEV-specific receptor and could not bind other betacoronavirus 1 spikes. This could be explained by large sequence variations between the RBD of PHEV and that of other members of the species, including BCoV or OC43.
jeremydufloo.bsky.social
Here, we show that contrary to other embecoviruses, the entry of PHEV does not require binding to sialic acid. In contrast, we identify dipeptidase 1 (DPEP1) as a functional PHEV receptor triggering PHEV spike-mediated fusion (entry and cell-cell fusion).
jeremydufloo.bsky.social
Therefore, sialic acid had long been considered as the only embecovirus receptor. However, the recent discovery that TMPRSS2 acts as the protein receptor of HKU1 revealed a more complex scenario. Whether other embecovirus dually depends on a protein and sialic acid is unknown.
jeremydufloo.bsky.social
The N-terminal domain (NTD) of the embecovirus spike harbors a conserved glycan-binding site that interacts with sialic acid in HKU1, OC43, BCoV, and PHEV and this interaction is necessary for HKU1, OC43 and BCoV entry.
jeremydufloo.bsky.social
The betacoronavirus 1 species is the main taxon of the Embecovirus subgenus (Betacoronavirus genus), which includes other relevant viruses such as the human common cold virus HKU1 🤒 and murine hepatitis virus (MHV) 🐁.
jeremydufloo.bsky.social
In this work, we focused on the betacoronavirus 1 species. It includes ten host-specific viruses such as the porcine hemagglutinating encephalomyelitis virus (PHEV) 🐖 and bovine coronavirus (BCoV) 🐄, but also the human seasonal cold virus OC43 🤒.
jeremydufloo.bsky.social
🚨 Preprint alter - bis 🚨

I am thrilled to share our last preprint where we identify and characterize a new coronavirus receptor! 🦠

This work was done in collaboration with the team of Félix Rey at the Institut Pasteur.

A 🧵 below...

www.biorxiv.org/content/10.1...
Dipeptidase 1 is a functional receptor for coronavirus PHEV
Coronaviruses of the subgenus Embecovirus include several relevant pathogens such as the human seasonal coronaviruses HKU1 and OC43, bovine coronavirus, and porcine hemagglutinating encephalomyelitis ...
www.biorxiv.org
jeremydufloo.bsky.social
🚨 New preprint alert 🚨

We searched for the presence of coronaviruses in >200 bat individuals across Spain 🦠🦇. We recovered 6 complete coronavirus genomes, including 3 novel species. One of them could use bat and human ACE2 for entry.

www.biorxiv.org/content/10.1...
Identification and characterization of novel bat coronaviruses in Spain
The zoonotic transmission of bat coronaviruses poses a threat to human health. However, the diversity of bat-borne coronaviruses remains poorly characterized in many geographical areas. Here, we recov...
www.biorxiv.org
jeremydufloo.bsky.social
I'd like to warmly thank everyone in Rafael Sanjuán's lab involved in this project! 🙏😃 I hope you'll enjoy the read, and don't hesitate to reach out if you're interested in any of the pseudotypes we generated! 😉
jeremydufloo.bsky.social
Altogether, our results suggest that post-entry stages of the infection cycle, as well as epidemiological and ecological factors, may be more critical determinants of viral zoonosis than entry.
jeremydufloo.bsky.social
We also tested the role of non-protein factors (i.e. sialic acids and heparan sulfates) in the entry of around 80 human-infective pseudotypes.