Gradauskaite, VaivaVaivaGradauskaiteKhosravi, MojtabaMojtabaKhosraviPlattet, PhilippePhilippePlattet2024-10-112024-10-112022-09https://boris-portal.unibe.ch/handle/20.500.12422/85382The envelope attachment (H)-protein of canine distemper virus (CDV) mediates receptor engagement and fusion-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-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.enSLAM receptor Wild-type CDV attachment protein H cell entry selective SLAM-blind Harticle10.48350/1703943564948310.1016/j.virusres.2022.198841