biostudies-literatureGradauskaite VSwiss National Science FoundationNovartis Stiftung für Medizinisch-Biologische ForschungEuropean Research CouncilAlbert Heim Foundatione0311422https://www.ebi.ac.uk/biostudies/studies/S-EPMC9973313biostudies-literatureUnknown14(1)Wild-type canine distemper virus (CDV) is an important pathogen of dogs as well as wildlife that can infect immune and epithelial cells through two known receptors: the signaling lymphocytic activation molecule (SLAM) and nectin-4, respectively. Conversely, the ferret and egg-adapted CDV-Onderstepoort strain (CDV-OP) is employed as an effective vaccine for dogs. CDV-OP also exhibits promising oncolytic properties, such as its abilities to infect and kill multiple cancer cells <i>in vitro</i>. Interestingly, several cancer cells do not express SLAM or nectin-4, suggesting the presence of a yet unknown entry factor for CDV-OP. By conducting a genome-wide CRISPR/Cas9 knockout (KO) screen in CDV-OP-susceptible canine mammary carcinoma P114 cells, which neither express SLAM nor nectin-4, we idemBioLRP6 Is a Functional Receptor for Attenuated Canine Distemper Virus.PMC9973313137AdG-8838771893378838773100030E_189337Scherer MDettwiler MPlattet PGradauskaite VShrestha NDoench JWyss MRottenberg SInglebert MfalseLRP6 Is a Functional Receptor for Attenuated Canine Distemper Virus.Wild-type canine distemper virus (CDV) is an important pathogen of dogs as well as wildlife that can infect immune and epithelial cells through two known receptors: the signaling lymphocytic activation molecule (SLAM) and nectin-4, respectively. Conversely, the ferret and egg-adapted CDV-Onderstepoort strain (CDV-OP) is employed as an effective vaccine for dogs. CDV-OP also exhibits promising oncolytic properties, such as its abilities to infect and kill multiple cancer cells <i>in vitro</i>. Interestingly, several cancer cells do not express SLAM or nectin-4, suggesting the presence of a yet unknown entry factor for CDV-OP. By conducting a genome-wide CRISPR/Cas9 knockout (KO) screen in CDV-OP-susceptible canine mammary carcinoma P114 cells, which neither express SLAM nor nectin-4, we ide2023-01-01T00:00:00Z2023 Feb2026-06-14T06:25:54.272Z2025-02-19T04:54:28.842ZS-EPMC99733133664530110.1128/mbio.03114-22