title: Adherens junction protein nectin-4 is the epithelial receptor for measles virus.
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.
authors: Division of Medical Biotechnology, Paul-Ehrlich-Institut, 63225 Langen, Germany.
authors: Michael D
authors: MD
authors: Mühlebach
authors: Mathieu
authors: M
authors: Mateo
authors: Patrick L
authors: PL
authors: Sinn
authors: Steffen
authors: S
authors: Prüfer
authors: Katharina M
authors: KM
authors: Uhlig
authors: Vincent H J
authors: VH
authors: Leonard
authors: Chanakha K
authors: CK
authors: Navaratnarajah
authors: Marie
authors: M
authors: Frenzke
authors: Xiao X
authors: XX
authors: Wong
authors: Bevan
authors: B
authors: Sawatsky
authors: Shyam
authors: S
authors: Ramachandran
authors: Paul B
authors: PB
authors: McCray
authors: Klaus
authors: K
authors: Cichutek
authors: Veronika
authors: V
authors: von Messling
authors: Marc
authors: M
authors: Lopez
authors: Roberto
authors: R
authors: Cattaneo
mesh_terms: D000818:Animals; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D020869:Gene Expression Profiling; D006801:Humans; D008457:Measles / Q000378:metabolism*; D008459:Measles virus / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D000075983:Nectins
chemical_list: D015815:Cell Adhesion Molecules; D011991:Receptors, Virus; C442228:NECTIN4 protein, human; D000075983:Nectins