Thanks Maria! 😀

Congratulations François !! 👏

Thanks Maria! 😊🙏🏻

Thanks a lot Spyros! Glad you liked them! 🙏🏻☺️

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! 📚

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.

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.

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.

Ignacio Fernández, from Félix Rey's lab, beautifully obtained the X-ray structure of DPEP1 in complex with the PHEV RBD.

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.

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).

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.

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.

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) 🐁.

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 🤒.

Thanks! 🙏🏻

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! 😉