Letter/Communication
Adherens junction protein nectin-4 is the epithelial receptor for measles virus
Nature, Vol.480(7378), pp.530-533
12/22/2011
DOI: 10.1038/nature10639
PMCID: PMC3245798
PMID: 22048310
Abstract
Measles virus is an aerosol-transmitted virus that affects more than 10 million children each year and accounts for approximately 120,000 deaths. Although it was long believed to replicate in the respiratory epithelium before disseminating, it was recently shown to infect initially macrophages and dendritic cells of the airways using signalling lymphocytic activation molecule family member 1 (SLAMF1; also called CD150) as a receptor. These cells then cross the respiratory epithelium and transport the infection to lymphatic organs where measles virus replicates vigorously. How and where the virus crosses back into the airways has remained unknown. On the basis of functional analyses of surface proteins preferentially expressed on virus-permissive human epithelial cell lines, here we identify nectin-4 (ref. 8; also called poliovirus-receptor-like-4 (PVRL4)) as a candidate host exit receptor. This adherens junction protein of the immunoglobulin superfamily interacts with the viral attachment protein with high affinity through its membrane-distal domain. Nectin-4 sustains measles virus entry and non-cytopathic lateral spread in well-differentiated primary human airway epithelial sheets infected basolaterally. It is downregulated in infected epithelial cells, including those of macaque tracheae. Although other viruses use receptors to enter hosts or transit through their epithelial barriers, we suggest that measles virus targets nectin-4 to emerge in the airways. Nectin-4 is a cellular marker of several types of cancer, which has implications for ongoing measles-virus-based clinical trials of oncolysis.
Details
- Title: Subtitle
- Adherens junction protein nectin-4 is the epithelial receptor for measles virus
- Creators
- Michael D Mühlebach - Division of Medical BiotechnologyPatrick L Sinn - Department of PediatricsMathieu Mateo - Department of Molecular MedicinePaul B McCray Jr - Department of PediatricsSteffen Prüfer - Division of Medical BiotechnologyKatharina M Uhlig - Division of Medical BiotechnologyVincent H J Leonard - Department of Molecular MedicineChanakha K Navaratnarajah - Department of Molecular MedicineMarie Frenzke - Department of Molecular MedicineXiao X Wong - Institut Armand FrappierBevan Sawatsky - Institut Armand FrappierShyam Ramachandran - Department of PediatricsKlaus Cichutek - Division of Medical BiotechnologyVeronika Von Messling - Institut Armand FrappierMarc Lopez - Centre de Recherche en Cancérologie de MarseilleRoberto Cattaneo - Department of Molecular Medicine
- Resource Type
- Letter/Communication
- Publication Details
- Nature, Vol.480(7378), pp.530-533
- DOI
- 10.1038/nature10639
- PMID
- 22048310
- PMCID
- PMC3245798
- NLM abbreviation
- Nature
- ISSN
- 0028-0836
- eISSN
- 1476-4679
- Publisher
- Nature Publishing Group
- Language
- English
- Date published
- 12/22/2011
- Academic Unit
- Microbiology and Immunology; Pulmonary Medicine; Stead Family Department of Pediatrics; Internal Medicine
- Record Identifier
- 9984093361402771
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