1. Adherens junction protein nectin-4 is the epithelial receptor for measles virus
- Author
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Chanakha K. Navaratnarajah, Xiao X. Wong, Veronika von Messling, Bevan Sawatsky, Michael D. Mühlebach, Steffen Prüfer, Roberto Cattaneo, Shyam Ramachandran, Katharina M. Uhlig, Patrick L. Sinn, Mathieu Mateo, Marie Frenzke, Paul B. McCray, Vincent H. J. Leonard, Klaus Cichutek, Marc Lopez, Division of Medical Biotechnology, Paul-Ehrlich-Institut, Department of Molecular Medicine, Mayo Clinic, Department of Pediatrics, University of Iowa [Iowa City]-Carver College of Medicine [Iowa City], University of Iowa [Iowa City], Institut Armand Frappier (INRS-IAF), Réseau International des Instituts Pasteur (RIIP)-Institut National de la Recherche Scientifique [Québec] (INRS), Duke University, National University of Singapore (NUS), Centre de Recherche en Cancérologie de Marseille (CRCM / U891 Inserm), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by grants BMG 2510-FSB-705 to M.D.M., NIH R01 AI063476 and NIH R01 CA090636 to R.C., the Roy J. Carver Charitable Trust, Cell Culture Core and Cell Morphology Cores, partially supported by the Center for Gene Therapy for Cystic Fibrosis (NIH P30 DK-54759), and the Cystic Fibrosis Foundation to P.B.M., and CIHR MOP-66989 and CFI 9488 to V.v.M., INSERM, Institut Paoli-Calmettes and the Ligue Nationale Contre le Cancer (label 2009-11) to M.L. X.X.W. was supported by a CIHR Master's Award., and Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP)
- Subjects
Virus genetics ,Paramyxoviridae ,MESH: Cricetinae ,CHO Cells ,Article ,Virus ,Cell Line ,Measles virus ,Adherens junction ,MESH: Gene Expression Profiling ,03 medical and health sciences ,0302 clinical medicine ,Morbillivirus ,MESH: CHO Cells ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Cricetinae ,Animals ,Humans ,MESH: Animals ,Mononegavirales ,030304 developmental biology ,0303 health sciences ,MESH: Humans ,Multidisciplinary ,biology ,Gene Expression Profiling ,biology.organism_classification ,MESH: Receptors, Virus ,Virology ,MESH: Cell Line ,3. Good health ,030220 oncology & carcinogenesis ,MESH: Cell Adhesion Molecules ,MESH: Measles ,Receptors, Virus ,Respiratory epithelium ,Cell Adhesion Molecules ,MESH: Measles virus ,Measles - Abstract
International audience; 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.
- Published
- 2011
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