title: Use of SLAM and PVRL4 and identification of pro-HB-EGF as cell entry receptors for wild type phocine distemper virus.
abstract: Signalling lymphocyte activation molecule (SLAM) has been identified as an immune cell receptor for the morbilliviruses, measles (MV), canine distemper (CDV), rinderpest and peste des petits ruminants (PPRV) viruses, while CD46 is a receptor for vaccine strains of MV. More recently poliovirus like receptor 4 (PVRL4), also known as nectin 4, has been identified as a receptor for MV, CDV and PPRV on the basolateral surface of polarised epithelial cells. PVRL4 is also up-regulated by MV in human brain endothelial cells. Utilisation of PVRL4 as a receptor by phocine distemper virus (PDV) remains to be demonstrated as well as confirmation of use of SLAM. We have observed that unlike wild type (wt) MV or wtCDV, wtPDV strains replicate in African green monkey kidney Vero cells without prior adaptation, suggesting the use of a further receptor. We therefore examined candidate molecules, glycosaminoglycans (GAG) and the tetraspan proteins, integrin β and the membrane bound form of heparin binding epithelial growth factor (proHB-EGF),for receptor usage by wtPDV in Vero cells. We show that wtPDV replicates in Chinese hamster ovary (CHO) cells expressing SLAM and PVRL4. Similar wtPDV titres are produced in Vero and VeroSLAM cells but more limited fusion occurs in the latter. Infection of Vero cells was not inhibited by anti-CD46 antibody. Removal/disruption of GAG decreased fusion but not the titre of virus. Treatment with anti-integrin β antibody increased rather than decreased infection of Vero cells by wtPDV. However, infection was inhibited by antibody to HB-EGF and the virus replicated in CHO-proHB-EGF cells, indicating use of this molecule as a receptor. Common use of SLAM and PVRL4 by morbilliviruses increases the possibility of cross-species infection. Lack of a requirement for wtPDV adaptation to Vero cells raises the possibility of usage of proHB-EGF as a receptor in vivo but requires further investigation.
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Melia
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: John Philip
authors.initials: JP
authors.lastname: Earle
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Haniah
authors.initials: H
authors.lastname: Abdullah
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Katherine
authors.initials: K
authors.lastname: Reaney
authors.affiliation: Viral Genomics and Vaccination Laboratory, Institut Pasteur, CNRS-URA3015, Paris, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Tangy
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Belfast, United Kingdom.
authors.forename: Sara Louise
authors.initials: SL
authors.lastname: Cosby
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003412:Cricetulus; D004216:Distemper / Q000235:genetics / Q000378:metabolism; D018104:Distemper Virus, Phocine / Q000502:physiology*; D004285:Dogs; D066257:Heparin-binding EGF-like Growth Factor / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D014709:Vero Cells; D053586:Virus Internalization
chemical_list: D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D066257:Heparin-binding EGF-like Growth Factor; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1