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Structural basis for VLDLR recognition by eastern equine encephalitis virus
Biorxiv : the Preprint Server for Biology
|November 28, 2023
Summary
Eastern equine encephalitis virus (EEEV) and Semliki forest virus (SFV) bind the same brain receptor, VLDLR, using distinct spike protein surfaces. This reveals divergent binding modes and a low evolutionary barrier for viruses using LDLR-related proteins as receptors.
Area of Science:
- Virology
- Structural Biology
- Neuroscience
Background:
- Alphaviruses are significant human pathogens transmitted by arthropods.
- Eastern equine encephalitis virus (EEEV) is a highly virulent alphavirus causing severe neurological sequelae.
- EEEV and Semliki forest virus (SFV) utilize brain-expressed very-low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as cellular entry receptors.
Conclusions:
- Different alphaviruses employ distinct molecular strategies to interact with the same cellular receptor.
- The flexible binding modes and small interaction footprints with LDLR-related proteins facilitate their adoption as receptors by diverse viruses.
- This adaptability suggests a low evolutionary barrier for viruses acquiring LDLR-family proteins as cellular receptors.
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