IDENTIFICATION OF A CYTOPLASMIC TYR-X-X-LEU MOTIF ESSENTIAL FOR DOWN-REGULATION OF THE HUMAN CELL-RECEPTOR CD46 IN PERSISTENT MEASLES-VIRUSINFECTION

To investigate the sequence requirements for measles virus (MV)-induce d receptor down regulation, we transfected the human CD46 gene into si mian cells persistently infected by; the Biken strain of MV. Surface e xpression of CD46 is drastically reduced in these cells. Deletion anal ysis has shown that the juxtamembrane region of the CD46 cytoplasmic d omain is essential for down regulation. Deleting a Tyr-Arg-Tyr-Leu seq uence in this region or changing these residues to Ala prevents CD46 d own regulation from the infected cell surface. Alanine-scanning mutage nesis has identified two amino acid residues, Tyr and Leu, forming a T yr-X-X-Leu motif critical for CD46 down regulation. Mutations that pre vent CD46 down regulation enhance syncytium formation. These results i ndicate that CD46 down regulation limits the cytopathic effects in a p ersistent MV infection and that CD46 down regulation requires a cytopl asmic Tyr-X-X-Leu sequence which resembles known motifs for membrane p rotein trafficking and receptor signalling.