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PXD060344
PXD060344 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | MFSD6 is an entry receptor for enterovirus D68 |
| Description | With the near eradication of poliovirus due to global vaccination campaigns, attention has shifted to other enteroviruses that can cause polio-like paralysis syndrome (now termed acute flaccid myelitis (AFM)). In particular, enterovirus D68 (EV-D68) is believed to be the main driver of epidemic outbreaks of AFM in recent years, yet not much is known about EV-D68 host interactions. EV-D68 is a respiratory virus but, in rare cases, can spread to the central nervous system to cause severe neuropathogenesis. Here, we use genome-scale CRISPR screens to identify the poorly characterized multipass membrane transporter MFSD6 as a host entry factor for EV-D68. Knockout of MFSD6 expression abrogates EV-D68 infection in cell lines and primary cells corresponding to respiratory and neural cells. MFSD6 is localized at the plasma membrane and is required for viral entry into the host cell. MFSD6 directly binds to EV-D68 particles via its third extracellular loop (L3). We determined the cryo-EM structure of EV-D68 in complex with L3 at 2.1 angstrom resolution, revealing the interaction interface. A decoy receptor, engineered by fusing MFSD6(L3) to Fc, blocked EV-D68 infection of human primary lung epithelial cells, and provided near complete protection in a lethal mouse model of EV-D68 infection. Collectively, our results reveal MFSD6 as an entry receptor for EV-D68, and support targeting MFSD6 as a potential mechanism to combat infections by this emerging pathogen with pandemic potential. |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-08-11 |
| AnnouncementXML | Submission_2026-08-11_10:24:48.227.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | David Roberts |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Hex3HexNAc2 |
| Instrument | 6230B Time-of-Flight LC/MS; Orbitrap Fusion ETD |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-01-29 17:35:22 | ID requested | |
| ⏵ 1 | 2026-08-11 10:24:49 | announced |
Publication List
| Varanese L, Xu L, Peters CE, Pintilie G, Roberts DS, Raj S, Liu M, Ooi YS, Diep J, Qiao W, Richards CM, Callaway J, Bertozzi CR, Jabs S, de Vries E, van Kuppeveld FJM, Nagamine CM, Chiu W, Carette JE, MFSD6 is an entry receptor for enterovirus D68. Nature, 641(8065):1268-1275(2025) [pubmed] |
Keyword List
| submitter keyword: MFSD6, Proteomics, Mucin, DatasetType:Proteomics |
Contact List
| Jan Carette | |
|---|---|
| contact affiliation | Stanford University |
| contact email | carette@stanford.edu |
| lab head | |
| David Roberts | |
| contact affiliation | Stanford University |
| contact email | dsroberts@stanford.edu |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive-ftp.ucsd.edu/v09/MSV000096996/ |
