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Keywords
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Wild-type CDV,Cell entry,SLAM receptor,Attachment protein H,
Selective SLAM-blind H
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Abstract
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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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