Adherens junction protein nectin-4 is the epithelial receptor for measles virus

Michael D. Mühlebach, Mathieu Mateo, Patrick L. Sinn, Steffen Prüfer, Katharina M. Uhlig, Vincent H J Leonard, Chanakha K. Navaratnarajah, Marie Frenzke, Xiao X. Wong, Bevan Sawatsky, Shyam Ramachandran, Paul B. McCray, Klaus Cichutek, Veronika Von Messling, Marc Lopez, Roberto Cattaneo

Research output: Contribution to journalArticle

324 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)530-533
Number of pages4
JournalNature
Volume480
Issue number7378
DOIs
StatePublished - Dec 22 2011

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Adherens Junctions
Measles virus
Respiratory Mucosa
Viruses
Proteins
Respiratory Transport
Epithelial Cells
Virus Receptors
Virus Internalization
Macaca
Viral Proteins
Trachea
Aerosols
Dendritic Cells
Immunoglobulins
Membrane Proteins
Down-Regulation
Macrophages
nectins
Clinical Trials

ASJC Scopus subject areas

  • General

Cite this

Mühlebach, M. D., Mateo, M., Sinn, P. L., Prüfer, S., Uhlig, K. M., Leonard, V. H. J., ... Cattaneo, R. (2011). Adherens junction protein nectin-4 is the epithelial receptor for measles virus. Nature, 480(7378), 530-533. https://doi.org/10.1038/nature10639

Adherens junction protein nectin-4 is the epithelial receptor for measles virus. / Mühlebach, Michael D.; Mateo, Mathieu; Sinn, Patrick L.; Prüfer, Steffen; Uhlig, Katharina M.; Leonard, Vincent H J; Navaratnarajah, Chanakha K.; Frenzke, Marie; Wong, Xiao X.; Sawatsky, Bevan; Ramachandran, Shyam; McCray, Paul B.; Cichutek, Klaus; Von Messling, Veronika; Lopez, Marc; Cattaneo, Roberto.

In: Nature, Vol. 480, No. 7378, 22.12.2011, p. 530-533.

Research output: Contribution to journalArticle

Mühlebach, MD, Mateo, M, Sinn, PL, Prüfer, S, Uhlig, KM, Leonard, VHJ, Navaratnarajah, CK, Frenzke, M, Wong, XX, Sawatsky, B, Ramachandran, S, McCray, PB, Cichutek, K, Von Messling, V, Lopez, M & Cattaneo, R 2011, 'Adherens junction protein nectin-4 is the epithelial receptor for measles virus', Nature, vol. 480, no. 7378, pp. 530-533. https://doi.org/10.1038/nature10639
Mühlebach MD, Mateo M, Sinn PL, Prüfer S, Uhlig KM, Leonard VHJ et al. Adherens junction protein nectin-4 is the epithelial receptor for measles virus. Nature. 2011 Dec 22;480(7378):530-533. https://doi.org/10.1038/nature10639
Mühlebach, Michael D. ; Mateo, Mathieu ; Sinn, Patrick L. ; Prüfer, Steffen ; Uhlig, Katharina M. ; Leonard, Vincent H J ; Navaratnarajah, Chanakha K. ; Frenzke, Marie ; Wong, Xiao X. ; Sawatsky, Bevan ; Ramachandran, Shyam ; McCray, Paul B. ; Cichutek, Klaus ; Von Messling, Veronika ; Lopez, Marc ; Cattaneo, Roberto. / Adherens junction protein nectin-4 is the epithelial receptor for measles virus. In: Nature. 2011 ; Vol. 480, No. 7378. pp. 530-533.
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