MFSD6 is an entry receptor for respiratory enterovirus D68.
Summary
The authors identify MFSD6 as a functional EV-D68 entry receptor that mediates viral attachment. An MFSD6-Fc recombinant decoy blocks uptake and infection in vitro and protects newborn mice from lethal challenge, highlighting a druggable entry mechanism.
Key Findings
- MFSD6 is necessary for EV-D68 attachment and supports viral replication.
- The second extracellular domain of MFSD6 mediates EV-D68 recognition.
- An MFSD6-Fc ectodomain decoy potently inhibits EV-D68 uptake and infection in vitro.
- MFSD6-Fc prevents lethality in EV-D68–challenged newborn mice.
Clinical Implications
Entry-blocking biologics such as MFSD6-Fc could be developed for prophylaxis or early treatment of EV-D68 outbreaks, especially in pediatric populations at risk for severe respiratory disease and acute flaccid myelitis.
Why It Matters
This is the first demonstration of MFSD6 as an EV-D68 entry factor with a translational decoy strategy that prevents lethality in vivo, opening avenues for antivirals against a major pediatric respiratory pathogen.
Limitations
- Preclinical study without human clinical validation.
- Breadth across EV-D68 clades and potential resistance pathways were not fully explored.
Future Directions
Validate MFSD6 dependency and MFSD6-Fc efficacy across EV-D68 clades, assess safety/pharmacokinetics, and explore synergy with neutralizing antibodies or small-molecule capsid binders.
Study Information
- Study Type
- Basic/Mechanistic
- Research Domain
- Pathophysiology
- Evidence Level
- V - Preclinical mechanistic study with in vitro assays and in vivo mouse efficacy.
- Study Design
- OTHER