西亚试剂：junction protein nectin-4 is the epithelial receptor for me

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

Michael D. Mühlebach1 Mathieu Mateo2 Patrick L. Sinn3 Steffen Prüfer1 Katharina M. Uhlig1 Vincent H. J. Leonard2 Chanakha K. Navaratnarajah2 Marie Frenzke2 Xiao X. Wong4 Bevan Sawatsky4 Shyam Ramachandran3 Paul B. McCray3 Klaus Cichutek1 Veronika von Messling4, 5 Marc Lopez6 Roberto Cattaneo2

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. ; 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. was measured in treated skin at the peak of UVB-induced hypersensitivity with custom-made