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  • Title: Selective SLAM/CD150 receptor-detargeting of canine distemper virus.
    Author: Gradauskaite V, Khosravi M, Plattet P.
    Journal: Virus Res; 2022 Sep; 318():198841. PubMed ID: 35649483.
    Abstract:
    The envelope attachment (H)-protein of canine distemper virus (CDV) mediates receptor engagement and fusion protein-triggering; two key functions in viral cell entry and spread. Signaling lymphocyte activation molecule (SLAM) and Nectin-4 (N4) act as morbilliviral entry receptors in immune and epithelial cells, respectively, which defines very similar pathogeneses. High incidence of brain disorders is however unique to CDV. The wild-type CDV-A75/17 strain (A75) preferentially infects glial cells and spreads from astrocyte-to-astrocyte without inducing massive fusion events, despite the fact that SLAM and N4 expressions remained below detection levels. To investigate whether an A75 H-microdomain required to interact with SLAM may additionally contribute to promote viral spread between astrocytes, we initially engineered a novel A75 H-protein variant (546-SYT/RNR-548) that lost SLAM-binding property and, consequently, lacked fusion protein-triggering activity specifically in SLAM-expressing cells. Collectively, this approach provides the molecular tool to decipher the role of the selected H-microdomain in supporting A75-spread in glial cells.
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